Evidence for miR-548c-5p regulation of FOXC2 transcription through a distal genomic target site in human podocytes.
Abstract Podocytes are highly differentiated epithelial cells outlining the glomerular vessels. FOXC2 is a transcription factor essential for inducing podocyte differentiation, development and maturation, and is considered to be the earliest podocyte marker. miRNA prediction analysis revealed a full-length target site for the primate-specific miR-548c-5p at a genomic region > 8 kb upstream of FOXC2. We hypothesised that the transcription rates of FOXC2 during podocyte differentiation might be tuned by miR-548c-5p through this target site. Experiments were performed with cultured human podocyt...
Source: Cellular and Molecular Life Sciences : CMLS - September 16, 2019 Category: Cytology Authors: Christofides A, Papagregoriou G, Dweep H, Makrides N, Gretz N, Felekkis K, Deltas C Tags: Cell Mol Life Sci Source Type: research

What is strain in neurodegenerative diseases?
Abstract Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are characterized by the aggregation of misfolded proteins, including Aβ, tau and α-synuclein. It is well recognized that these misfolded proteins are able to self-propagate and spread throughout the nervous system and cause neuronal injury in a way that resembles prion disease. These disease-specific misfolded proteins demonstrate unique features, including the seeding barrier, the conformational memory effect, strain selection and strain evolution, based on the presence of various strains. However, the accurate d...
Source: Cellular and Molecular Life Sciences : CMLS - September 16, 2019 Category: Cytology Authors: Tian Y, Meng L, Zhang Z Tags: Cell Mol Life Sci Source Type: research

Current perspective on the regulation of FOXO4 and its role in disease progression.
Abstract Forkhead box O4 (FOXO4) is a member of the FOXO family that regulates a number of genes involved in metabolism, cell cycle, apoptosis, and cellular homeostasis via transcriptional activity. It also mediates cell responses to oxidative stress and treatment with antitumor agents. The expression of FOXO4 is repressed by microRNAs in multiple cancer cells, while FOXO4 function is regulated by post-translational modifications and interaction with other proteins. The deregulation of FOXO4 is closely linked to the progression of several types of cancer, senescence, and other diseases. In this review, we present ...
Source: Cellular and Molecular Life Sciences : CMLS - September 15, 2019 Category: Cytology Authors: Liu W, Li Y, Luo B Tags: Cell Mol Life Sci Source Type: research

Auditory function and dysfunction: estrogen makes a difference.
oix L Abstract Estrogen is the major female hormone involved in reproductive functions, but it also exerts a variety of additional roles in non-reproductive organs. In this review, we highlight the preclinical and clinical studies that have pointed out sex differences and estrogenic influence on audition. We also describe the experimental evidences supporting a protective role of estrogen towards acquired forms of hearing loss. Although a high level of endogenous estrogen is associated with a better hearing function, hormonal treatments at menopause have provided contradictory outcomes. The various factors that ar...
Source: Cellular and Molecular Life Sciences : CMLS - September 13, 2019 Category: Cytology Authors: Delhez A, Lefebvre P, Péqueux C, Malgrange B, Delacroix L Tags: Cell Mol Life Sci Source Type: research

Histone demethylase KDM4A regulates adipogenic and osteogenic differentiation via epigenetic regulation of C/EBP α and canonical Wnt signaling.
Histone demethylase KDM4A regulates adipogenic and osteogenic differentiation via epigenetic regulation of C/EBPα and canonical Wnt signaling. Cell Mol Life Sci. 2019 Sep 12;: Authors: Qi Q, Wang Y, Wang X, Yang J, Xie Y, Zhou J, Li X, Wang B Abstract Epigenetic modifications play a central role in cell differentiation and development. In the current study, we have recognized lysine demethylase 4A (KDM4A) as a novel epigenetic regulator of osteoblast and adipocyte differentiation. Kdm4a expression was upregulated during osteogenesis and adipogenesis of primary marrow stromal cells and establishe...
Source: Cellular and Molecular Life Sciences : CMLS - September 11, 2019 Category: Cytology Authors: Qi Q, Wang Y, Wang X, Yang J, Xie Y, Zhou J, Li X, Wang B Tags: Cell Mol Life Sci Source Type: research

Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications.
Abstract Gap junctions consist of arrays of intercellular channels that enable adjacent cells to communicate both electrically and metabolically. Gap junctions have a wide diversity of physiological functions, playing critical roles in both excitable and non-excitable tissues. Gap junction channels are formed by integral membrane proteins called connexins. Inherited or acquired alterations in connexins are associated with numerous diseases, including heart failure, neuropathologies, deafness, skin disorders, cataracts and cancer. Gap junctions are highly dynamic structures and by modulating the turnover rate of co...
Source: Cellular and Molecular Life Sciences : CMLS - September 8, 2019 Category: Cytology Authors: Totland MZ, Rasmussen NL, Knudsen LM, Leithe E Tags: Cell Mol Life Sci Source Type: research

Toxoplasma gondii ROP16 kinase silences the cyclin B1 gene promoter by hijacking host cell UHRF1-dependent epigenetic pathways.
This study demonstrates that Toxoplasma hijacks a new epigenetic initiator, UHRF1, through an early event initiated by the ROP16 parasite kinase. PMID: 31492965 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - September 5, 2019 Category: Cytology Authors: Sabou M, Doderer-Lang C, Leyer C, Konjic A, Kubina S, Lennon S, Rohr O, Viville S, Cianférani S, Candolfi E, Pfaff AW, Brunet J Tags: Cell Mol Life Sci Source Type: research

The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic resumption by targeting PTEN degradation.
In this study, we demonstrated that DCAF13 stimulates the meiotic resumption-coupled activation of protein synthesis in oocytes, partially by maintaining the activity of PI3K signaling pathway. CRL4-DCAF13 targets the polyubiquitination and degradation of PTEN, a lipid phosphatase that inhibits PI3K pathway as well as oocyte growth and maturation. Dcaf13 knockout in oocytes caused decreased CDK1 activity and impaired meiotic cell cycle progression and chromosome condensation defects. As a result, chromosomes fail to be aligned at the spindle equatorial plate, the spindle assembly checkpoint is activated, and most Dcaf13 nu...
Source: Cellular and Molecular Life Sciences : CMLS - September 5, 2019 Category: Cytology Authors: Zhang J, Zhang YL, Zhao LW, Pi SB, Zhang SY, Tong C, Fan HY Tags: Cell Mol Life Sci Source Type: research

Stoichiometry and regulation network of Bcl-2 family complexes quantified by live-cell FRET assay.
Abstract The stoichiometry and affinity of Bcl-2 family complexes are essential information for understanding how their interactome network is orchestrated to regulate mitochondrial permeabilization and apoptosis. Based on over-expression model system, FRET analysis was used to quantify the protein-protein interactions among Bax, Bcl-xL, Bad and tBid in healthy and apoptotic cells. Our data indicate that the stoichiometry and affinity of Bcl-2 complexes are dependent on their membrane environment. Bcl-xL, Bad and tBid can form hetero-trimers in mitochondria. Bcl-xL binds preferentially to Bad, then to tBid and Bax...
Source: Cellular and Molecular Life Sciences : CMLS - September 5, 2019 Category: Cytology Authors: Yang F, Qu W, Du M, Mai Z, Wang B, Ma Y, Wang X, Chen T Tags: Cell Mol Life Sci Source Type: research

MicroRNA-24-3p regulates neuronal differentiation by controlling hippocalcin expression.
Abstract Hippocalcin (HPCA) is a neuron-specific calcium-binding protein predominantly expressed in the nervous system. In the present study, we demonstrate that HPCA regulates neuronal differentiation in SH-SY5Y cells. We observed that the expression level of HPCA was increased during neuronal differentiation. Depletion of HPCA inhibited both neurite outgrowth and synaptophysin (SYP) expression, whereas overexpression of HPCA enhanced neuronal differentiation. Interestingly, we also found that the expression of HPCA mRNA was modulated by miR-24-3p. Using a dual-luciferase assay, we showed that co-transfection of ...
Source: Cellular and Molecular Life Sciences : CMLS - September 4, 2019 Category: Cytology Authors: Kang MJ, Park SY, Han JS Tags: Cell Mol Life Sci Source Type: research

Structural and functional analysis of "non-smelly" proteins.
Structural and functional analysis of "non-smelly" proteins. Cell Mol Life Sci. 2019 Sep 05;: Authors: Yan J, Cheng J, Kurgan L, Uversky VN Abstract Cysteine and aromatic residues are major structure-promoting residues. We assessed the abundance, structural coverage, and functional characteristics of the "non-smelly" proteins, i.e., proteins that do not contain cysteine residues (C-depleted) or cysteine and aromatic residues (CFYWH-depleted), across 817 proteomes from all domains of life. The analysis revealed that although these proteomes contained significant levels of the C-depl...
Source: Cellular and Molecular Life Sciences : CMLS - September 4, 2019 Category: Cytology Authors: Yan J, Cheng J, Kurgan L, Uversky VN Tags: Cell Mol Life Sci Source Type: research

Sialic acid-binding immunoglobulin-like lectins (Siglecs) detect self-associated molecular patterns to regulate immune responses.
i A Abstract The mammalian immune system evolved to tightly regulate the elimination of pathogenic microbes and neoplastic transformed cells while tolerating our own healthy cells. Here, we summarize experimental evidence for the role of Siglecs-in particular CD33-related Siglecs-as self-receptors and their sialoglycan ligands in regulating this balance between recognition of self and non-self. Sialoglycans are found in the glycocalyx and extracellular fluids and matrices of all mammalian cells and can be considered as self-associated molecular patterns (SAMPs). We also provide an overview of the known interaction...
Source: Cellular and Molecular Life Sciences : CMLS - September 3, 2019 Category: Cytology Authors: Läubli H, Varki A Tags: Cell Mol Life Sci Source Type: research

Insights from Drosophila on mitochondrial complex I.
Abstract NADH:ubiquinone oxidoreductase, more commonly referred to as mitochondrial complex I (CI), is the largest discrete enzyme of the oxidative phosphorylation system (OXPHOS). It is localized to the mitochondrial inner membrane. CI oxidizes NADH generated from the tricarboxylic acid cycle to NAD+, in a series of redox reactions that culminates in the reduction of ubiquinone, and the transport of protons from the matrix across the inner membrane to the intermembrane space. The resulting proton-motive force is consumed by ATP synthase to generate ATP, or harnessed to transport ions, metabolites and proteins int...
Source: Cellular and Molecular Life Sciences : CMLS - September 3, 2019 Category: Cytology Authors: Rhooms SK, Murari A, Goparaju NSV, Vilanueva M, Owusu-Ansah E Tags: Cell Mol Life Sci Source Type: research

Knockdown of Foxg1 in supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse cochlea.
Abstract Foxg1 is one of the forkhead box genes that are involved in morphogenesis, cell fate determination, and proliferation, and Foxg1 was previously reported to be required for morphogenesis of the mammalian inner ear. However, Foxg1 knock-out mice die at birth, and thus the role of Foxg1 in regulating hair cell (HC) regeneration after birth remains unclear. Here we used Sox2CreER/+ Foxg1loxp/loxp mice and Lgr5-EGFPCreER/+ Foxg1loxp/loxp mice to conditionally knock down Foxg1 specifically in Sox2+ SCs and Lgr5+ progenitors, respectively, in neonatal mice. We found that Foxg1 conditional knockdown (cKD) in Sox2...
Source: Cellular and Molecular Life Sciences : CMLS - September 3, 2019 Category: Cytology Authors: Zhang S, Zhang Y, Dong Y, Guo L, Zhang Z, Shao B, Qi J, Zhou H, Zhu W, Yan X, Hong G, Zhang L, Zhang X, Tang M, Zhao C, Gao X, Chai R Tags: Cell Mol Life Sci Source Type: research

Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular Ca2+ signals and nitric oxide release in human brain microvascular endothelial cells.
Abstract Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity causes an increase in local cerebral blood flow (CBF) to ensure local supply of oxygen and nutrients to the activated areas. The excitatory neurotransmitter glutamate gates post-synaptic N-methyl-D-aspartate receptors to mediate extracellular Ca2+ entry and stimulate neuronal nitric oxide (NO) synthase to release NO, thereby triggering NVC. Recent work suggested that endothelial Ca2+ signals could underpin NVC by recruiting the endothelial NO synthase. For instance, acetylcholine induced intracellular Ca2+ signals follo...
Source: Cellular and Molecular Life Sciences : CMLS - August 30, 2019 Category: Cytology Authors: Negri S, Faris P, Pellavio G, Botta L, Orgiu M, Forcaia G, Sancini G, Laforenza U, Moccia F Tags: Cell Mol Life Sci Source Type: research

Apolipoprotein E-mediated regulation of selenoprotein P transportation via exosomes.
Abstract Selenoprotein P (SELENOP), secreted from the liver, functions as a selenium (Se) supplier to other tissues. In the brain, Se homeostasis is critical for physiological function. Previous studies have reported that SELENOP co-localizes with the apolipoprotein E receptor 2 (ApoER2) along the blood-brain barrier (BBB). However, the mechanism underlying SELENOP transportation from hepatocytes to neuronal cells remains unclear. Here, we found that SELENOP was secreted from hepatocytes as an exosomal component protected from plasma kallikrein-mediated cleavage. SELENOP was interacted with apolipoprotein E (ApoE)...
Source: Cellular and Molecular Life Sciences : CMLS - August 29, 2019 Category: Cytology Authors: Jin Y, Chung YW, Jung MK, Lee JH, Ko KY, Jang JK, Ham M, Kang H, Pack CG, Mihara H, Kim IY Tags: Cell Mol Life Sci Source Type: research

Mechanisms of resistance to estrogen receptor modulators in ER+/HER2- advanced breast cancer.
Abstract Endocrine therapy represents a mainstay adjuvant treatment of estrogen receptor-positive (ER+) breast cancer in clinical practice with an overall survival (OS) benefit. However, the emergence of resistance is inevitable over time and is present in one-third of the ER+ breast tumors. Several mechanisms of endocrine resistance in ER+/HER2- advanced breast cancers, through ERα itself, receptor tyrosine signaling, or cell cycle pathway, have been identified to be pivotal in endocrine therapy. The epigenetic alterations also contribute to ensuring tumor cells' escape from endocrine therapie...
Source: Cellular and Molecular Life Sciences : CMLS - August 29, 2019 Category: Cytology Authors: Zhang J, Wang Q, Wang Q, Cao J, Sun J, Zhu Z Tags: Cell Mol Life Sci Source Type: research

Placental mesenchymal stromal cells as an alternative tool for therapeutic angiogenesis.
Abstract Dysregulation of angiogenesis is a phenomenon observed in several disorders such as diabetic foot, critical limb ischemia and myocardial infarction. Mesenchymal stromal cells (MSCs) possess angiogenic potential and have recently emerged as a powerful tool for cell therapy to promote angiogenesis. Although bone marrow-derived MSCs are the primary cell of choice, obtaining them has become a challenge. The placenta has become a popular alternative as it is a highly vascular organ, easily available and ethically more favorable with a rich supply of MSCs. Comparatively, placenta-derived MSCs (PMSCs) are clinic...
Source: Cellular and Molecular Life Sciences : CMLS - August 28, 2019 Category: Cytology Authors: Mathew SA, Naik C, Cahill PA, Bhonde RR Tags: Cell Mol Life Sci Source Type: research

Drug repurposing studies of PARP inhibitors as a new therapy for inherited retinal degeneration.
Abstract The enzyme poly-ADP-ribose-polymerase (PARP) has important roles for many forms of DNA repair and it also participates in transcription, chromatin remodeling and cell death signaling. Currently, some PARP inhibitors are approved for cancer therapy, by means of canceling DNA repair processes and cell division. Drug repurposing is a new and attractive aspect of therapy development that could offer low-cost and accelerated establishment of new treatment options. Excessive PARP activity is also involved in neurodegenerative diseases including the currently untreatable and blinding retinitis pigmentosa group o...
Source: Cellular and Molecular Life Sciences : CMLS - August 25, 2019 Category: Cytology Authors: Sahaboglu A, Miranda M, Canjuga D, Avci-Adali M, Savytska N, Secer E, Feria-Pliego JA, Kayık G, Durdagi S Tags: Cell Mol Life Sci Source Type: research

Tetraspanin1 promotes NGF signaling by controlling TrkA receptor proteostasis.
Abstract The molecular mechanisms that control the biosynthetic trafficking, surface delivery, and degradation of TrkA receptor are essential for proper nerve growth factor (NGF) function, and remain poorly understood. Here, we identify Tetraspanin1 (Tspan1) as a critical regulator of TrkA signaling and neuronal differentiation induced by NGF. Tspan1 is expressed by developing TrkA-positive dorsal root ganglion (DRG) neurons and its downregulation in sensory neurons inhibits NGF-mediated axonal growth. In addition, our data demonstrate that Tspan1 forms a molecular complex with the immature form of TrkA localized ...
Source: Cellular and Molecular Life Sciences : CMLS - August 21, 2019 Category: Cytology Authors: Ferrero Restelli F, Fontanet PA, De Vincenti AP, Falzone TL, Ledda F, Paratcha G Tags: Cell Mol Life Sci Source Type: research

Copper-mediated thiol potentiation and mutagenesis-guided modeling suggest a highly conserved copper-binding motif in human OR2M3.
Abstract Sulfur-containing compounds within a physiological relevant, natural odor space, such as the key food odorants, typically constitute the group of volatiles with the lowest odor thresholds. The observation that certain metals, such as copper, potentiate the smell of sulfur-containing, metal-coordinating odorants led to the hypothesis that their cognate receptors are metalloproteins. However, experimental evidence is sparse-so far, only one human odorant receptor, OR2T11, and a few mouse receptors, have been reported to be activated by sulfur-containing odorants in a copper-dependent way, while the activati...
Source: Cellular and Molecular Life Sciences : CMLS - August 20, 2019 Category: Cytology Authors: Haag F, Ahmed L, Reiss K, Block E, Batista VS, Krautwurst D Tags: Cell Mol Life Sci Source Type: research

G-protein βγ subunits as multi-functional scaffolds and transducers in G-protein-coupled receptor signaling.
G-protein βγ subunits as multi-functional scaffolds and transducers in G-protein-coupled receptor signaling. Cell Mol Life Sci. 2019 Aug 21;: Authors: Smrcka AV, Fisher I Abstract G-protein βγ subunits are key participants in G-protein signaling. These subunits facilitate interactions between receptors and G proteins that are critical for the G protein activation cycle at the plasma membrane. In addition, they play roles in directly transducing signals to an ever expanding range of downstream targets, including integral membrane and cytosolic proteins. Emerging data indicate that...
Source: Cellular and Molecular Life Sciences : CMLS - August 20, 2019 Category: Cytology Authors: Smrcka AV, Fisher I Tags: Cell Mol Life Sci Source Type: research

The enhancement of glycolysis regulates pancreatic cancer metastasis.
Abstract Pancreatic ductal adenocarcinoma is prone to distant metastasis and is expected to become the second leading cause of cancer-related death. In an extremely nutrient-deficient and hypoxic environment resulting from uncontrolled growth, vascular disturbances and desmoplastic reactions, pancreatic cancer cells utilize "metabolic reprogramming" to satisfy their energy demand and support malignant behaviors such as metastasis. Notably, pancreatic cancer cells show extensive enhancement of glycolysis, including glycolytic enzyme overexpression and increased lactate production, and this is caused by mi...
Source: Cellular and Molecular Life Sciences : CMLS - August 19, 2019 Category: Cytology Authors: Yang J, Ren B, Yang G, Wang H, Chen G, You L, Zhang T, Zhao Y Tags: Cell Mol Life Sci Source Type: research

Insights into the mechanisms of epilepsy from structural biology of LGI1-ADAM22.
Abstract Epilepsy is one of the most common brain disorders, which can be caused by abnormal synaptic transmissions. Many epilepsy-related mutations have been identified in synaptic ion channels, which are main targets for current antiepileptic drugs. One of the novel potential targets for therapy of epilepsy is a class of non-ion channel-type epilepsy-related proteins. The leucine-rich repeat glioma-inactivated protein 1 (LGI1) is a neuronal secreted protein, and has been extensively studied as a product of a causative gene for autosomal dominant lateral temporal lobe epilepsy (ADLTE; also known as autosomal domi...
Source: Cellular and Molecular Life Sciences : CMLS - August 19, 2019 Category: Cytology Authors: Yamagata A, Fukai S Tags: Cell Mol Life Sci Source Type: research

G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub.
yor F Abstract Accumulating evidence indicates that G protein-coupled receptor kinase 2 (GRK2) is a versatile protein that acts as a signaling hub by modulating G protein-coupled receptor (GPCR) signaling and also via phosphorylation or scaffolding interactions with an extensive number of non-GPCR cellular partners. GRK2 multifunctionality arises from its multidomain structure and from complex mechanisms of regulation of its expression levels, activity, and localization within the cell, what allows the precise spatio-temporal shaping of GRK2 targets. A better understanding of the GRK2 interactome and its modulatio...
Source: Cellular and Molecular Life Sciences : CMLS - August 19, 2019 Category: Cytology Authors: Penela P, Ribas C, Sánchez-Madrid F, Mayor F Tags: Cell Mol Life Sci Source Type: research

Understanding protein multifunctionality: from short linear motifs to cellular functions.
Abstract Moonlighting proteins perform multiple unrelated functions without any change in polypeptide sequence. They can coordinate cellular activities, serving as switches between pathways and helping to respond to changes in the cellular environment. Therefore, regulation of the multiple protein activities, in space and time, is likely to be important for the homeostasis of biological systems. Some moonlighting proteins may perform their multiple functions simultaneously while others alternate between functions due to certain triggers. The switch of the moonlighting protein's functions can be regulated by severa...
Source: Cellular and Molecular Life Sciences : CMLS - August 19, 2019 Category: Cytology Authors: Zanzoni A, Ribeiro DM, Brun C Tags: Cell Mol Life Sci Source Type: research

Molecular switches for regulating the differentiation of inflammatory and IL-10-producing anti-inflammatory T-helper cells.
Abstract CD4 T-helper (Th) cells secret a variety of inflammatory cytokines and play critical roles in host defense against invading foreign pathogens. On the other hand, uncontrolled inflammatory responses mediated by Th cells may result in tissue damage and inflammatory disorders including autoimmune and allergic diseases. Thus, the induction of anti-inflammatory cytokine expression becomes an important "brake" to repress and/or terminate aberrant and/or unnecessary immune responses. Interleukin-10 (IL-10) is one of the most important anti-inflammatory cytokines to limit inflammatory Th cells and immun...
Source: Cellular and Molecular Life Sciences : CMLS - August 19, 2019 Category: Cytology Authors: Fang D, Zhu J Tags: Cell Mol Life Sci Source Type: research

Multi-functionality of proteins involved in GPCR and G protein signaling: making sense of structure-function continuum with intrinsic disorder-based proteoforms.
Abstract GPCR-G protein signaling system recognizes a multitude of extracellular ligands and triggers a variety of intracellular signaling cascades in response. In humans, this system includes more than 800 various GPCRs and a large set of heterotrimeric G proteins. Complexity of this system goes far beyond a multitude of pair-wise ligand-GPCR and GPCR-G protein interactions. In fact, one GPCR can recognize more than one extracellular signal and interact with more than one G protein. Furthermore, one ligand can activate more than one GPCR, and multiple GPCRs can couple to the same G protein. This defines an intric...
Source: Cellular and Molecular Life Sciences : CMLS - August 18, 2019 Category: Cytology Authors: Fonin AV, Darling AL, Kuznetsova IM, Turoverov KK, Uversky VN Tags: Cell Mol Life Sci Source Type: research

Organization and dynamics of functional plant membrane microdomains.
Abstract Plasma membranes are heterogeneous and laterally compartmentalized into distinct microdomains. These membrane microdomains consist of special lipids and proteins and are thought to act as signaling platforms. In plants, membrane microdomains have been detected by super-resolution microscopy, and there is evidence that they play roles in several biological processes. Here, we review current knowledge about the lipid and protein components of membrane microdomains. Furthermore, we summarize the dynamics of membrane microdomains in response to different stimuli. We also explore the biological functions assoc...
Source: Cellular and Molecular Life Sciences : CMLS - August 16, 2019 Category: Cytology Authors: Yu M, Cui Y, Zhang X, Li R, Lin J Tags: Cell Mol Life Sci Source Type: research

Protein multi-functionality: introduction.
Abstract The five articles in this multi-author review in CMLS provide examples of multi-functionality of proteins belonging to several families. Distinct structural features of proteins suggesting multi-functionality are emphasized: intrinsically disordered elements that can "mold" themselves to fit various binding partners, as well as short linear motifs within larger proteins that perform particular functions. Although only a few protein families are discussed in detail, the conclusions apply to numerous, if not all, proteins. Multi-functionality of virtually every protein implies that the manipulatio...
Source: Cellular and Molecular Life Sciences : CMLS - August 16, 2019 Category: Cytology Authors: Gurevich VV Tags: Cell Mol Life Sci Source Type: research

Plethora of functions packed into 45  kDa arrestins: biological implications and possible therapeutic strategies.
Plethora of functions packed into 45 kDa arrestins: biological implications and possible therapeutic strategies. Cell Mol Life Sci. 2019 Aug 17;: Authors: Gurevich VV, Gurevich EV Abstract Mammalian arrestins are a family of four highly homologous relatively small ~ 45 kDa proteins with surprisingly diverse functions. The most striking feature is that each of the two non-visual subtypes can bind hundreds of diverse G protein-coupled receptors (GPCRs) and dozens of non-receptor partners. Through these interactions, arrestins regulate the G protein-dependent signaling by the dese...
Source: Cellular and Molecular Life Sciences : CMLS - August 16, 2019 Category: Cytology Authors: Gurevich VV, Gurevich EV Tags: Cell Mol Life Sci Source Type: research

Atypical cyclins: the extended family portrait.
Abstract Regulation of cell division is orchestrated by cyclins, which bind and activate their catalytic workmates, the cyclin-dependent kinases (CDKs). Cyclins have been traditionally defined by an oscillating (cyclic) pattern of expression and by the presence of a characteristic "cyclin box" that determines binding to the CDKs. Noteworthy, the Human Genome Sequence Project unveiled the existence of several other proteins containing the "cyclin box" domain. These potential "cyclins" have been named new, orphan or atypical, creating a conundrum in cyclins nomenclature. Moreover, altho...
Source: Cellular and Molecular Life Sciences : CMLS - August 15, 2019 Category: Cytology Authors: Quandt E, Ribeiro MPC, Clotet J Tags: Cell Mol Life Sci Source Type: research

Mechanisms and significance of therapy-induced and spontaneous senescence of cancer cells.
Abstract In contrast to the well-recognized replicative and stress-induced premature senescence of normal somatic cells, mechanisms and clinical implications of senescence of cancer cells are still elusive and uncertain from patient-oriented perspective. Moreover, recent years provided multiple pieces of evidence that cancer cells may undergo senescence not only in response to chemotherapy or ionizing radiation (the so-called therapy-induced senescence) but also spontaneously, without any external insults. Since the molecular nature of the latter process is poorly recognized, the significance of spontaneously sene...
Source: Cellular and Molecular Life Sciences : CMLS - August 13, 2019 Category: Cytology Authors: Mikuła-Pietrasik J, Niklas A, Uruski P, Tykarski A, Książek K Tags: Cell Mol Life Sci Source Type: research

Farnesoid X receptor alpha (FXR α) is a critical actor of the development and pathologies of the male reproductive system.
Farnesoid X receptor alpha (FXRα) is a critical actor of the development and pathologies of the male reproductive system. Cell Mol Life Sci. 2019 Aug 12;: Authors: Garcia M, Thirouard L, Monrose M, Holota H, De Haze A, Caira F, Beaudoin C, Volle DH Abstract The farnesoid-X-receptorα (FXRα; NR1H4) is one of the main bile acid (BA) receptors. During the last decades, through the use of pharmalogical approaches and transgenic mouse models, it has been demonstrated that the nuclear receptor FXRα controls numerous physiological functions such as glucose or energy metabolisms. I...
Source: Cellular and Molecular Life Sciences : CMLS - August 11, 2019 Category: Cytology Authors: Garcia M, Thirouard L, Monrose M, Holota H, De Haze A, Caira F, Beaudoin C, Volle DH Tags: Cell Mol Life Sci Source Type: research

Smad linker region phosphorylation is a signalling pathway in its own right and not only a modulator of canonical TGF- β signalling.
Smad linker region phosphorylation is a signalling pathway in its own right and not only a modulator of canonical TGF-β signalling. Cell Mol Life Sci. 2019 Aug 12;: Authors: Kamato D, Do BH, Osman N, Ross BP, Mohamed R, Xu S, Little PJ Abstract Transforming growth factor (TGF)-β signalling pathways are intensively investigated because of their diverse association with physiological and pathophysiological states. Smad transcription factors are the key mediators of TGF-β signalling. Smads can be directly phosphorylated in the carboxy terminal by the TGF-β receptor or in the linker re...
Source: Cellular and Molecular Life Sciences : CMLS - August 11, 2019 Category: Cytology Authors: Kamato D, Do BH, Osman N, Ross BP, Mohamed R, Xu S, Little PJ Tags: Cell Mol Life Sci Source Type: research

Compensatory increase of VE-cadherin expression through ETS1 regulates endothelial barrier function in response to TNF α.
Compensatory increase of VE-cadherin expression through ETS1 regulates endothelial barrier function in response to TNFα. Cell Mol Life Sci. 2019 Aug 08;: Authors: Colás-Algora N, García-Weber D, Cacho-Navas C, Barroso S, Caballero A, Ribas C, Correas I, Millán J Abstract VE-cadherin plays a central role in controlling endothelial barrier function, which is transiently disrupted by proinflammatory cytokines such as tumor necrosis factor (TNFα). Here we show that human endothelial cells compensate VE-cadherin degradation in response to TNFα by inducing VE-cadherin ...
Source: Cellular and Molecular Life Sciences : CMLS - August 7, 2019 Category: Cytology Authors: Colás-Algora N, García-Weber D, Cacho-Navas C, Barroso S, Caballero A, Ribas C, Correas I, Millán J Tags: Cell Mol Life Sci Source Type: research

Translation of TNFAIP2 is tightly controlled by upstream open reading frames.
chmid T Abstract Translation is a highly regulated process, both at the global as well as on a transcript-specific level. Regulatory upstream open reading frames (uORFs) represent a mode to alter cap-dependent translation efficiency in a transcript-specific manner and are found in numerous mRNAs. In the majority of cases, uORFs inhibit the translation of their associated main ORFs. Consequently, their inactivation results in enhanced translation of the main ORF, a phenomenon best characterized in the context of the integrated stress response. In the present study, we identified potent translation-inhibitory uORFs ...
Source: Cellular and Molecular Life Sciences : CMLS - August 6, 2019 Category: Cytology Authors: Scholz A, Rappl P, Böffinger N, Mota AC, Brüne B, Schmid T Tags: Cell Mol Life Sci Source Type: research

ERCC1-XPF targeting to psoralen-DNA crosslinks depends on XPA and FANCD2.
Abstract The effectiveness of many DNA-damaging chemotherapeutic drugs depends on their ability to form monoadducts, intrastrand crosslinks and/or interstrand crosslinks (ICLs) that interfere with transcription and replication. The ERCC1-XPF endonuclease plays a critical role in removal of these lesions by incising DNA either as part of nucleotide excision repair (NER) or interstrand crosslink repair (ICLR). Engagement of ERCC1-XPF in NER is well characterized and is facilitated by binding to the XPA protein. However, ERCC1-XPF recruitment to ICLs is less well understood. Moreover, specific mutations in XPF have b...
Source: Cellular and Molecular Life Sciences : CMLS - August 6, 2019 Category: Cytology Authors: Sabatella M, Pines A, Slyskova J, Vermeulen W, Lans H Tags: Cell Mol Life Sci Source Type: research

Lipophagy mediated carbohydrate-induced changes of lipid metabolism via oxidative stress, endoplasmic reticulum (ER) stress and ChREBP/PPAR γ pathways.
In this study, we investigated the role of autophagy in the process of HCD-induced changes of hepatic lipid metabolism, and to examine the process of underlying mechanisms during these molecular contexts. We found that HCD significantly increased hepatic lipid accumulation and activated autophagy. Using primary hepatocytes, we found that HG increased lipid accumulation and stimulated the release of NEFA by autophagy-mediated lipophagy, and that lipophagy significantly alleviated high glucose (HG)-induced lipid accumulation. Oxidative and endoplasmic reticulum (ER) stress pathways played crucial regulatory roles in HG-induc...
Source: Cellular and Molecular Life Sciences : CMLS - August 6, 2019 Category: Cytology Authors: Zhao T, Wu K, Hogstrand C, Xu YH, Chen GH, Wei CC, Luo Z Tags: Cell Mol Life Sci Source Type: research

Distinct effects of etoposide on glutamine-addicted neuroblastoma.
Abstract The majority of anticancer drugs are DNA-damaging agents, and whether or not they may directly target mitochondria remains unclear. In addition, tumors such as neuroblastoma exhibit addiction to glutamine in spite of it being a nonessential amino acid. Our aim was to evaluate the direct effect of widely used anticancer drugs on mitochondrial activity in combination with glutamine withdrawal, and possible apoptotic effects of such interaction. Our results revealed that etoposide inhibits mitochondrial respiratory chain Complex I causing the leakage of electrons and the superoxide radical formation. However...
Source: Cellular and Molecular Life Sciences : CMLS - August 6, 2019 Category: Cytology Authors: Valter K, Maximchik P, Abdrakhmanov A, Senichkin V, Zhivotovsky B, Gogvadze V Tags: Cell Mol Life Sci Source Type: research

Glutamate controls vessel-associated migration of GABA interneurons from the pial migratory route via NMDA receptors and endothelial protease activation.
This study supports that glutamate controls the vessel-associated migration of GABA interneurons by regulating the activity of endothelial proteases. This effect requires endothelial NMDAR and is t-PA-dependent. These neurodevelopmental data reinforce the debate regarding safety of molecules with NMDA-antagonist properties administered to preterm and term neonates. PMID: 31392351 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - August 6, 2019 Category: Cytology Authors: Léger C, Dupré N, Aligny C, Bénard M, Lebon A, Henry V, Hauchecorne M, Galas L, Frebourg T, Leroux P, Vivien D, Lecointre M, Marret S, Gonzalez BJ Tags: Cell Mol Life Sci Source Type: research

Non-peptidyl small molecule, adenosine, 5'-Se-methyl-5'-seleno-, 2',3'-diacetate, activates insulin receptor and attenuates hyperglycemia in type 2 diabetic Leprdb/db mice.
Abstract The pathophysiology of type 2 diabetes mellitus (T2D) is characterized by reduced or absent insulin receptor (INSR) responsiveness to its ligand, elevated hepatic glucose output and impaired glucose uptake in peripheral tissues, particularly skeletal muscle. Treatments to reduce hyperglycemia and reestablish normal insulin signaling are much sought after. Any agent which could be orally administered to restore INSR function, in an insulin-independent manner, would have major implications for the management of this global disease. We have discovered a non-peptidyl small molecule, adenosine, 5'-Se-methyl-5'...
Source: Cellular and Molecular Life Sciences : CMLS - August 4, 2019 Category: Cytology Authors: Lan ZJ, Lei Z, Yiannikouris A, Yerramreddy TR, Li X, Kincaid H, Eastridge K, Gadberry H, Power C, Xiao R, Lei L, Seale O, Dawson K, Power R Tags: Cell Mol Life Sci Source Type: research

Correction to: Monitoring activities of receptor tyrosine kinases using a universal adapter in genetically encoded split TEV assays.
Abstract The article Monitoring activities of receptor tyrosine kinases using a universal adapter in genetically encoded split TEV assays, written by Jan P. Wintgens, Sven P. Wichert, Luksa Popovic, Moritz J. Rossner and Michael C. Wehr, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 8 January 2019 without open access. PMID: 31377842 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - August 2, 2019 Category: Cytology Authors: Wintgens JP, Wichert SP, Popovic L, Rossner MJ, Wehr MC Tags: Cell Mol Life Sci Source Type: research

Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management.
Abstract Infertility is a global health problem involving about 15% of couples. Approximately half of the infertility cases are related to male factors. The oxidative stress, which refers to an imbalance in levels of reactive oxygen species (ROS) and antioxidants, is one of the main causes of infertility in men. A small amount of ROS is necessary for the physiological function of sperm including the capacitation, hyperactivation and acrosomal reaction. However, high levels of ROS can cause infertility through not only by lipid peroxidation or DNA damage but inactivation of enzymes and oxidation of proteins in sper...
Source: Cellular and Molecular Life Sciences : CMLS - August 2, 2019 Category: Cytology Authors: Barati E, Nikzad H, Karimian M Tags: Cell Mol Life Sci Source Type: research

Dual CCR5/CCR2 targeting: opportunities for the cure of complex disorders.
Abstract The chemokine system mediates acute inflammation by driving leukocyte migration to damaged or infected tissues. However, elevated expression of chemokines and their receptors can contribute to chronic inflammation and malignancy. Thus, great effort has been taken to target these molecules. The first hint of the druggability of the chemokine system was derived from the role of chemokine receptors in HIV infection. CCR5 and CXCR4 function as essential co-receptors for HIV entry, with the former accounting for most new HIV infections worldwide. Not by chance, an anti-CCR5 compound, maraviroc, was the first F...
Source: Cellular and Molecular Life Sciences : CMLS - August 2, 2019 Category: Cytology Authors: Fantuzzi L, Tagliamonte M, Gauzzi MC, Lopalco L Tags: Cell Mol Life Sci Source Type: research

DCTPP1 prevents a mutator phenotype through the modulation of dCTP, dTTP and dUTP pools.
González-Pacanowska D Abstract To maintain dNTP pool homeostasis and preserve genetic integrity of nuclear and mitochondrial genomes, the synthesis and degradation of DNA precursors must be precisely regulated. Human all-alpha dCTP pyrophosphatase 1 (DCTPP1) is a dNTP pyrophosphatase with high affinity for dCTP and 5'-modified dCTP derivatives, but its contribution to overall nucleotide metabolism is controversial. Here, we identify a central role for DCTPP1 in the homeostasis of dCTP, dTTP and dUTP. Nucleotide pools and the dUTP/dTTP ratio are severely altered in DCTPP1-deficient cells, which exhibit an a...
Source: Cellular and Molecular Life Sciences : CMLS - August 2, 2019 Category: Cytology Authors: Martínez-Arribas B, Requena CE, Pérez-Moreno G, Ruíz-Pérez LM, Vidal AE, González-Pacanowska D Tags: Cell Mol Life Sci Source Type: research

The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with valines and intron reservoirs.
We described the origin and evolutionary history of 9aaTADs. The 9aaTADs of the ancestral Sp2 gene became inactivated in early chordates. We next discovered that an accumulation of valines in 9aaTADs inactivated their transactivation function and enabled their strict conservation during evolution. Subsequently, in chordates, Sp2 has duplicated and created new paralogs, Sp1, Sp3, and Sp4 (the SP1-4 clade). During chordate evolution, the dormancy of the Sp2 activation domain lasted over 100 million years. The dormant but still intact ancestral Sp2 activation domains allowed diversification of the SP1-4 clade into activators ...
Source: Cellular and Molecular Life Sciences : CMLS - August 1, 2019 Category: Cytology Authors: Piskacek M, Havelka M, Jendruchova K, Knight A, Keegan LP Tags: Cell Mol Life Sci Source Type: research

Two of a kind: transmissible Schwann cell cancers in the endangered Tasmanian devil (Sarcophilus harrisii).
In this study, we compared the transcriptome and proteome of DFT2 tumours to DFT1 and normal Tasmanian devil tissues to determine the tissue-of-origin of the DFT2 cancer. Our findings demonstrate that DFT2 expresses a range of Schwann cell markers and exhibits expression patterns consistent with a similar origin to the DFT1 cancer. Furthermore, DFT2 cells express genes associated with the repair response to peripheral nerve damage. These findings suggest that devils may be predisposed to transmissible cancers of Schwann cell origin. The combined effect of factors such as frequent nerve damage from biting, Schwann cell plas...
Source: Cellular and Molecular Life Sciences : CMLS - August 1, 2019 Category: Cytology Authors: Patchett AL, Coorens THH, Darby J, Wilson R, McKay MJ, Kamath KS, Rubin A, Wakefield M, Mcintosh L, Mangiola S, Pye RJ, Flies AS, Corcoran LM, Lyons AB, Woods GM, Murchison EP, Papenfuss AT, Tovar C Tags: Cell Mol Life Sci Source Type: research

Leishmania heme uptake involves LmFLVCRb, a novel porphyrin transporter essential for the parasite.
ute;n JJG, Pérez-Victoria JM Abstract Leishmaniasis comprises a group of neglected diseases caused by the protozoan parasite Leishmania spp. As is the case for other trypanosomatid parasites, Leishmania is auxotrophic for heme and must scavenge this essential compound from its human host. In mammals, the SLC transporter FLVCR2 mediates heme import across the plasma membrane. Herein we identify and characterize Leishmania major FLVCRb (LmFLVCRb), the first member of the FLVCR family studied in a non-metazoan organism. This protein localizes to the plasma membrane of the parasite and is able to bind heme. LmF...
Source: Cellular and Molecular Life Sciences : CMLS - July 31, 2019 Category: Cytology Authors: Cabello-Donayre M, Orrego LM, Herráez E, Vargas P, Martínez-García M, Campos-Salinas J, Pérez-Victoria I, Vicente B, Marín JJG, Pérez-Victoria JM Tags: Cell Mol Life Sci Source Type: research

Programmable RNA manipulation in living cells.
Abstract RNAs are responsible for mediating genetic information flow within the cell. RNA splicing, modification, trafficking, translation, and stability are all controlled at the transcript level. However, biological tools to study and manipulate them in a programmable fashion are currently limited. In this review, we summarize recent advances regarding available RNA-targeting systems discovered so far, including CRISPR-based technologies-Cas9 and Cas13, and programmable RNA-binding proteins-PUF and PPR. These tools allow transcript-specific manipulation in gene expression. PMID: 31367845 [PubMed - as suppli...
Source: Cellular and Molecular Life Sciences : CMLS - July 30, 2019 Category: Cytology Authors: Pei Y, Lu M Tags: Cell Mol Life Sci Source Type: research