The gelatinase biosynthesis ‐activating pheromone binds and stabilises the FsrB membrane protein in Enterococcus faecalis quorum sensing
Quorum ‐sensing mechanisms regulate gene expression in response to changing cell‐population density detected through pheromones. InEnterococcus  faecalis, Fsr quorum sensing produces and responds to the gelatinase biosynthesis ‐activating pheromone (GBAP). Here we establish that the enterococcal FsrB membrane protein has a direct role connected with GBAP by showing that GBAP binds to purified FsrB. Far‐UV CD measurements demonstrated a predominantly α‐helical protein exhibiting a small level of conformational flexi bility. Fivefold (400 μm) GBAP stabilised FsrB (80  μm) secondary struct...
Source: FEBS Letters - October 21, 2019 Category: Biochemistry Authors: Sean Littlewood, Helena Tattersall, Charlotte S. Hughes, Rohanah Hussain, Pikyee Ma, Stephen E. Harding, Jiro Nakayama, Mary K. Phillips ‐Jones Tags: Communication Source Type: research

Human ‐induced pluripotent stem cell‐derived blood products: state of the art and future directions
In  vitro cultured blood cells for transfusion purposes provide a safe alternative to donor blood, particularly for patients who require recurrent transfusions, and can be used as carriers of therapeutic molecules.In  vitro derivation of hematopoietic cell types from human ‐induced pluripotent stem cells (iPSCs) allows for a constant, well‐defined production pipeline for such advanced therapeutic and medicinal products. Application of selected iPSC‐derived hematopoietic stem cells and hematopoietic effector cells in transplantation/transfusions would avoid the r isk of alloimmunization and blood‐borne dis...
Source: FEBS Letters - October 20, 2019 Category: Biochemistry Authors: Marten Hansen, Marieke von Lindern, Emile van den Akker, Eszter Varga Tags: Review Article Source Type: research

Impacts of deletion and ichthyosis prematurity syndrome ‐associated mutations in fatty acid transport protein 4 on the function of RPE65
The retinal pigment epithelium ‐specific 65 kDa (RPE65) isomerase plays a pivotal role in photoreceptor survival and function. RPE65‐catalyzed synthesis of 11‐cis‐retinol from all‐trans‐retinyl esters in the visual cycle is negatively regulated, through a heretofore unknown mechanism, by the fatty acid transport protein FATP4, mutations in which are associated with ichthyosis prematurity syndrome (IPS). Here, we analyzed the interaction between deletion mutants of FATP4 and RPE6 5 and the impacts of IPS‐associated FATP4 mutations on RPE65 expression, 11‐cis‐retinol synthesis, and all‐trans‐retiny...
Source: FEBS Letters - October 20, 2019 Category: Biochemistry Authors: Songhua Li, John F. Green, Minghao Jin Tags: Research Letter Source Type: research

Voltage ‐gated sodium channels β3 subunit promotes tumorigenesis in hepatocellular carcinoma by facilitating p53 degradation
AbstractThe Voltage ‐gated sodium channels (VGSCs) are aberrantly expressed in a variety of tumors and play an important role in tumor growth and metastasis. Here, we show that VGSCs auxiliary β3 subunit, encoded by theSCN3B gene, promotes proliferation and suppresses apoptosis in HepG2 cells by promoting p53 degradation. β3 significantly increases HepG2 cell proliferation, promotes tumor growth in mouse xenograft models, and suppresses senescence and apoptosis. We found that β3 knockdown stabilizes p53 protein, leading to potentiation of p53‐induced cell cycle arrest, senescence and apoptosis. Mechanist...
Source: FEBS Letters - October 18, 2019 Category: Biochemistry Authors: Shuai Li, Jiadi Han, Guili Guo, Yudi Sun, Tingting Zhang, Mingyi Zhao, Yijia Xu, Yong Cui, Yanfeng Liu, Jinghai Zhang Tags: RESEARCH LETTER Source Type: research

A missense mutation in the catalytic domain of O ‐GlcNAc transferase links perturbations in protein O‐GlcNAcylation to X‐linked intellectual disability
AbstractX ‐linked Intellectual Disabilities (XLID) are common developmental disorders. The enzymeO‐GlcNAc transferase encoded byOGT, a recently discovered XLID gene, attachesO‐GlcNAc to nuclear and cytoplasmic proteins. As few missense mutations have been described, it is unclear what the aetiology of the patient phenotypes is. Here, we report the discovery of a missense mutation in the catalytic domain of OGT in an XLID patient. X‐ray crystallography reveals that th is variant leads to structural rearrangements in the catalytic domain. The mutation reducesin vitro OGT activity on substrate peptides/protein. Mouse ...
Source: FEBS Letters - October 18, 2019 Category: Biochemistry Authors: Veronica M. Pravata, Mehmet Gundogdu, Sergio G. Bartual, Andrew T. Ferenbach, Marios Stavridis, Katrin Õunap, Sander Pajusalu, Riina Žordania, Monica H. Wojcik, Daan M.F. van Aalten Tags: RESEARCH LETTER Source Type: research

Inhibition of Chikungunya virus by an Adenosine Analog targeting the SAM ‐dependent nsP1 methyltransferase
AbstractAlphaviruses, including Chikungunya (CHIKV) and Venezuelan equine encephalitis virus (VEEV), are among the leading causes of recurrent epidemics all over the world. Alphaviral non ‐structural protein 1 (nsP1) orchestrates the capping of nascent viral RNA via its S‐adenosyl methionine‐dependent N‐7‐methyltransferase (MTase) and guanylyltransferase activities. Here, we developed and validated a novel capillary electrophoresis (CE)‐based assay for measuring the MTase activity of purified VEEV and CHIKV nsP1. We employed the assay to assess the MTase inhibition efficiency of a few adenosine analogs and iden...
Source: FEBS Letters - October 17, 2019 Category: Biochemistry Authors: Rajat Mudgal, Supreeti Mahajan, Shailly Tomar Tags: RESEARCH ARTICLES Source Type: research

Front Cover
Cover illustration The cover image is taken from the article “The glycoprotein mucin‐1 negatively regulates GalNAc transferase 5 expression in pancreatic cancer” by T. Caffreyet al. (pp.2751 –2761). (Source: FEBS Letters)
Source: FEBS Letters - October 14, 2019 Category: Biochemistry Tags: Issue Information Source Type: research

Illuminating the membrane contact sites between the endoplasmic reticulum and the trans ‐Golgi network
AbstractMembrane contact sites (MCSs) between different organelles have been identified and extensively studied over the last decade. Several classes of MCSs have now well ‐established roles, but the contacts between the endoplasmic reticulum (ER) and the trans‐side of the Golgi network (TGN) have long remained elusive. Until recently, the study of ER‐TGN contact sites has represented a major challenge in the field, due to the lack of suitable visualization and isolation techniques. Only in the last five years, a combination of advanced technologies and innovative approaches has permitted the identification of new mo...
Source: FEBS Letters - October 14, 2019 Category: Biochemistry Authors: Maria Chiara Masone, Valentina Morra, Rossella Venditti Tags: REVIEW Source Type: research

Front Cover
Cover illustration The cover image is taken from the article “The glycoprotein mucin‐1 negatively regulates GalNAc transferase 5 expression in pancreatic cancer” by T. Caffreyet al. (pp.2751 –2761). (Source: FEBS Letters)
Source: FEBS Letters - October 14, 2019 Category: Biochemistry Tags: Issue Information Source Type: research

Illuminating the membrane contact sites between the endoplasmic reticulum and the trans ‐Golgi network
AbstractMembrane contact sites (MCSs) between different organelles have been identified and extensively studied over the last decade. Several classes of MCSs have now well ‐established roles, but the contacts between the endoplasmic reticulum (ER) and the trans‐side of the Golgi network (TGN) have long remained elusive. Until recently, the study of ER‐TGN contact sites has represented a major challenge in the field, due to the lack of suitable visualization and isolation techniques. Only in the last five years, a combination of advanced technologies and innovative approaches has permitted the identification of new mo...
Source: FEBS Letters - October 14, 2019 Category: Biochemistry Authors: Maria Chiara Masone, Valentina Morra, Rossella Venditti Tags: REVIEW Source Type: research

Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic coculture
Transcription factor (TF) ‐based reprogramming of somatic tissues holds great promise for regenerative medicine. Previously, we demonstrated that the TFs GATA2, GFI1B, and FOS convert mouse and human fibroblasts to hemogenic endothelial‐like precursors that generate hematopoietic stem progenitor (HSPC)‐like cells over time. This conversion is lacking in robustness both in yield and biological function. Herein, we show that inclusion of GFI1 to the reprogramming cocktail significantly expands the HSPC‐like population. AFT024 coculture imparts functional potential to these cells and allows quantification of stem cell...
Source: FEBS Letters - October 12, 2019 Category: Biochemistry Authors: Michael G. Daniel, David Sachs, Jeffrey M. Bernitz, Yesai Fstkchyan, Katrina Rapp, Namita Satija, Kenneth Law, Foram Patel, Andreia M. Gomes, Huen ‐Suk Kim, Carlos‐Filipe Pereira, Benjamin Chen, Ihor R. Lemischka, Kateri A. Moore Tags: Research Article Source Type: research

Ligand ‐dependent intra‐ and interdomain motions in the PDZ12 tandem regulate binding interfaces in postsynaptic density protein‐95
The postsynaptic density protein ‐95 (PSD‐95) regulates synaptic plasticity through interactions mediated by its peptide‐binding PDZ domains. The two N‐terminal PDZ domains of PSD‐95 form an autonomous structural unit, and their interdomain orientation and dynamics depend on ligand binding. To understand the mechanistic d etails of the effect of ligand binding, we generated conformational ensembles using available experimentally determined nuclear Overhauser effect interatomic distances and S2 order parameters. In our approach, the fast dynamics of the two domains is treated independently. We find that intradomai...
Source: FEBS Letters - October 12, 2019 Category: Biochemistry Authors: Bertalan Kov ács, Nóra Zajácz‐Epresi, Zoltán Gáspári Tags: Research Letter Source Type: research

A small molecule chaperone rescues the stability and activity of a cancer ‐associated variant of NAD(P)H:quinone oxidoreductase 1 in vitro
In this study, we show that a small molecular chaperone (N‐(2‐bromophenyl)pyrrolidine‐1‐sulfonamide) repopulates the native wild‐type conformation. As a consequence of th e stabilizing effect, the enzymatic activity of the P187S variant protein is strongly improved in the presence of the molecular chaperonein vitro. (Source: FEBS Letters)
Source: FEBS Letters - October 12, 2019 Category: Biochemistry Authors: Emilia Strandback, Wolf ‐Dieter Lienhart, Altijana Hromic‐Jahjefendic, Benjamin Bourgeois, Anja Högler, Daniel Waltenstorfer, Andreas Winkler, Klaus Zangger, Tobias Madl, Karl Gruber, Peter Macheroux Tags: RESEARCH ARTICLES Source Type: research

Ligand ‐dependent intra‐ and interdomain motions in the PDZ12 tandem regulate binding interfaces in postsynaptic density protein‐95
The postsynaptic density protein ‐95 (PSD‐95) regulates synaptic plasticity through interactions mediated by its peptide‐binding PDZ domains. The two N‐terminal PDZ domains of PSD‐95 form an autonomous structural unit, and their interdomain orientation and dynamics depend on ligand binding. To understand the mechanistic d etails of the effect of ligand binding, we generated conformational ensembles using available experimentally determined nuclear Overhauser effect interatomic distances and S2 order parameters. In our approach, the fast dynamics of the two domains is treated independently. We find that intradomai...
Source: FEBS Letters - October 12, 2019 Category: Biochemistry Authors: Bertalan Kov ács, Nóra Zajácz‐Epresi, Zoltán Gáspári Tags: Research Letter Source Type: research

A small molecule chaperone rescues the stability and activity of a cancer ‐associated variant of NAD(P)H:quinone oxidoreductase 1 in vitro
In this study, we show that a small molecular chaperone (N‐(2‐bromophenyl)pyrrolidine‐1‐sulfonamide) repopulates the native wild‐type conformation. As a consequence of th e stabilizing effect, the enzymatic activity of the P187S variant protein is strongly improved in the presence of the molecular chaperonein vitro. (Source: FEBS Letters)
Source: FEBS Letters - October 12, 2019 Category: Biochemistry Authors: Emilia Strandback, Wolf ‐Dieter Lienhart, Altijana Hromic‐Jahjefendic, Benjamin Bourgeois, Anja Högler, Daniel Waltenstorfer, Andreas Winkler, Klaus Zangger, Tobias Madl, Karl Gruber, Peter Macheroux Tags: RESEARCH ARTICLES Source Type: research

Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic coculture
Transcription factor (TF) ‐based reprogramming of somatic tissues holds great promise for regenerative medicine. Previously, we demonstrated that the TFs GATA2, GFI1B, and FOS convert mouse and human fibroblasts to hemogenic endothelial‐like precursors that generate hematopoietic stem progenitor (HSPC)‐like cells over time. This conversion is lacking in robustness both in yield and biological function. Herein, we show that inclusion of GFI1 to the reprogramming cocktail significantly expands the HSPC‐like population. AFT024 coculture imparts functional potential to these cells and allows quantification of stem cell...
Source: FEBS Letters - October 12, 2019 Category: Biochemistry Authors: Michael G. Daniel, David Sachs, Jeffrey M. Bernitz, Yesai Fstkchyan, Katrina Rapp, Namita Satija, Kenneth Law, Foram Patel, Andreia M. Gomes, Huen ‐Suk Kim, Carlos‐Filipe Pereira, Benjamin Chen, Ihor R. Lemischka, Kateri A. Moore Tags: Research Article Source Type: research

Hijacking intracellular membranes to feed autophagosomal growth
AbstractAutophagy is widely considered as a housekeeping mechanism enabling cells to survive stress conditions and, in particular, nutrient deprivation. Autophagy begins with the formation of the phagophore that expands and closes around cytosolic material and damaged organelles destined for degradation. The execution of this complex machinery is guaranteed by the coordinated action of more than 40 ATG (Autophagy ‐related) proteins that control the entire process at different stages from the biogenesis of the autophagosome to cargo sequestration and fusion with lysosomes. Autophagosome biogenesis occurs at multiple intra...
Source: FEBS Letters - October 11, 2019 Category: Biochemistry Authors: Leopoldo Staiano, Francesca Zappa Tags: Review Source Type: research

The Gelatinase Biosynthesis ‐Activating Pheromone binds and stabilizes the FsrB membrane protein in Enterococcus faecalis quorum sensing
AbstractQuorum sensing mechanisms regulate gene expression in response to changing cell ‐population density detected through pheromones. InEnterococcus faecalis, Fsr quorum sensing produces and responds to the gelatinase biosynthesis ‐activating pheromone (GBAP). Here, we establish that the enterococcal FsrB membrane protein has a direct role connected with GBAP by showing that GBAP binds to purified FsrB. Far‐UV circular dichroism measurements demonstrated a predominantly α‐helical protein exhibiting a small level of con formational flexibility. Five‐fold (400 µM) GBAP stabilised FsrB (80 µM) s...
Source: FEBS Letters - October 10, 2019 Category: Biochemistry Authors: Sean Littlewood, Helena Tattersall, Charlotte S. Hughes, Rohanah Hussain, Pikyee Ma, Stephen E. Harding, Jiro Nakayama, Mary K. Phillips ‐Jones Tags: Communication Source Type: research

Triggering Mitosis
AbstractEntry into mitosis is triggered by the activation of Cdk1. This simple reaction rapidly and irreversibly sets the cell up for division. Even though the core step in triggering mitosis is so simple, the regulation of this cellular switch is highly complex, involving a large number of interconnected signalling cascades. We do have a detailed knowledge of most of the components of this network, but only a poor understanding of how they work together to create a precise and robust system that ensures that mitosis is triggered at the right time and in an orderly fashion. In this review we will give an overview of the li...
Source: FEBS Letters - October 10, 2019 Category: Biochemistry Authors: Adrijana Crncec, Helfrid Hochegger Tags: REVIEW Source Type: research

The Gelatinase Biosynthesis ‐Activating Pheromone binds and stabilizes the FsrB membrane protein in Enterococcus faecalis quorum sensing
AbstractQuorum sensing mechanisms regulate gene expression in response to changing cell ‐population density detected through pheromones. InEnterococcus faecalis, Fsr quorum sensing produces and responds to the gelatinase biosynthesis ‐activating pheromone (GBAP). Here, we establish that the enterococcal FsrB membrane protein has a direct role connected with GBAP by showing that GBAP binds to purified FsrB. Far‐UV circular dichroism measurements demonstrated a predominantly α‐helical protein exhibiting a small level of con formational flexibility. Five‐fold (400 µM) GBAP stabilised FsrB (80 µM) s...
Source: FEBS Letters - October 10, 2019 Category: Biochemistry Authors: Sean Littlewood, Helena Tattersall, Charlotte S. Hughes, Rohanah Hussain, Pikyee Ma, Stephen E. Harding, Jiro Nakayama, Mary K. Phillips ‐Jones Tags: Communication Source Type: research

Chlamydia  trachomatis‐infected human cells convert ceramide to sphingomyelin without sphingomyelin synthases 1 and 2
The obligate intracellular bacteriumChlamydia  trachomatis proliferates in the membranous compartment inclusion formed in host cells. The host ceramide transport protein CERT delivers ceramide from the endoplasmic reticulum to the Golgi complex for the synthesis of sphingomyelin (SM).Chlamydia  trachomatis has been suggested to employ CERT to produce SM in the inclusion by host SM synthases (SMSs). Here, we found thatC.  trachomatis proliferates and produces infective progeny even inSMS1 andSMS2 double ‐knockout HeLa cells, but not in theSMS1/SMS2/CERT triple ‐knockout cells. Interestingly, infected cell...
Source: FEBS Letters - October 9, 2019 Category: Biochemistry Authors: Yuriko Tachida, Keigo Kumagai, Shota Sakai, Shuji Ando, Toshiyuki Yamaji, Kentaro Hanada Tags: Research Letter Source Type: research

Chlamydia trachomatis ‐infected human cells convert ceramide to sphingomyelin without sphingomyelin synthases 1 and 2
AbstractThe obligate intracellular bacteriumChlamydia trachomatis proliferates in the membranous compartment inclusion formed in host cells. The host ceramide transport protein CERT delivers ceramide from the endoplasmic reticulum to the Golgi complex for the synthesis of sphingomyelin (SM).C. trachomatis has been suggested to employ CERT to produce SM in the inclusion by host SM synthases (SMSs). Here, we found thatC. trachomatis proliferates and produces infective progeny even inSMS1 andSMS2 double knockout HeLa cells, but not in theSMS1/SMS2/CERT triple knockout cells. Interestingly, infected cells convert ceramide to S...
Source: FEBS Letters - October 9, 2019 Category: Biochemistry Authors: Yuriko Tachida, Keigo Kumagai, Shota Sakai, Shuji Ando, Toshiyuki Yamaji, Kentaro Hanada Tags: Research Letter Source Type: research

Enterococcus  faecalis α1–2‐mannosidase (EfMan‐I): an efficient catalyst for glycoprotein N‐glycan modification
We report here the characterization and crystal structure of a new α1–2‐mannosidase (EfMan‐I) fromEnterococcus  faecalis, a Gram ‐positive opportunistic human pathogen. EfMan‐I catalyzes the cleavage of α1–2‐mannose from not only oligomannoses but also high‐mannose‐type N‐glycans on glycoproteins. Its 2.15 Å resolution crystal structure reveals a two‐domain enzyme fold similar to other CAZy GH92 mannosidase s. An unexpected potassium ion was observed bridging two domains near the active site. These findings support EfMan‐I as an effective catalyst forin  vitr...
Source: FEBS Letters - October 8, 2019 Category: Biochemistry Authors: Yanhong Li, Riyao Li, Hai Yu, Xue Sheng, Jing Wang, Andrew J. Fisher, Xi Chen Tags: Research Article Source Type: research

Impacts of deletion and ichthyosis prematurity syndrome (IPS) ‐associated mutations in fatty acid transport protein 4 (FATP4) on the function of RPE65
AbstractThe retinal pigment epithelium ‐specific 65 kDa (RPE65) isomerase plays a pivotal role in photoreceptor survival and function. RPE65‐catalyzed synthesis of 11‐cis‐retinol from all‐trans‐retinyl esters in the visual cycle is negatively regulated, through a heretofore unknown mechanism, by the fatty acid transport protein FATP4, mutations in which are associated with ichthyosis prematurity syndrome (IPS). Here, we analyzed the interaction between deletion mutants of FATP4 and RPE6 5 as well as the impacts of IPS‐associated FATP4 mutations on RPE65 expression, 11‐cis‐retinol synthesis, and all‐tran...
Source: FEBS Letters - October 8, 2019 Category: Biochemistry Authors: Songhua Li, John F. Green, Minghao Jin Tags: Research Letter Source Type: research

Stabilization of soluble high ‐affinity T‐cell receptor with de novo disulfide bonds
Soluble T ‐cell receptors (TCRs) have recently gained visibility as target‐recognition units of anticancer immunotherapeutic agents. Here, we improved the thermal stability of the well‐expressed high‐affinity A6 TCR by introducing pairs of cysteines in the invariable parts of the α‐ and β‐chain. A mutant with a novel intradomain disulfide bond in each chain also tested superior to the wild‐type in the accelerated stability assay. Binding of the mutant to the soluble cognate peptide (cp)–MHC and to the peptide‐loaded T2 cell line was equal to the wild‐type A6 TCR. The same stabiliza tion m...
Source: FEBS Letters - October 8, 2019 Category: Biochemistry Authors: Fl ávio Sádio, Gerhard Stadlmayr, Katharina Stadlbauer, Maximilian Gräf, Agnes Scharrer, Florian Rüker, Gordana Wozniak‐Knopp Tags: Research Article Source Type: research

Enterococcus  faecalis α1–2‐mannosidase (EfMan‐I): an efficient catalyst for glycoprotein N‐glycan modification
We report here the characterization and crystal structure of a new α1–2‐mannosidase (EfMan‐I) fromEnterococcus  faecalis, a Gram ‐positive opportunistic human pathogen. EfMan‐I catalyzes the cleavage of α1–2‐mannose from not only oligomannoses but also high‐mannose‐type N‐glycans on glycoproteins. Its 2.15 Å resolution crystal structure reveals a two‐domain enzyme fold similar to other CAZy GH92 mannosidase s. An unexpected potassium ion was observed bridging two domains near the active site. These findings support EfMan‐I as an effective catalyst forin  vitr...
Source: FEBS Letters - October 8, 2019 Category: Biochemistry Authors: Yanhong Li, Riyao Li, Hai Yu, Xue Sheng, Jing Wang, Andrew J. Fisher, Xi Chen Tags: Research Article Source Type: research

Impacts of deletion and ichthyosis prematurity syndrome (IPS) ‐associated mutations in fatty acid transport protein 4 (FATP4) on the function of RPE65
AbstractThe retinal pigment epithelium ‐specific 65 kDa (RPE65) isomerase plays a pivotal role in photoreceptor survival and function. RPE65‐catalyzed synthesis of 11‐cis‐retinol from all‐trans‐retinyl esters in the visual cycle is negatively regulated, through a heretofore unknown mechanism, by the fatty acid transport protein FATP4, mutations in which are associated with ichthyosis prematurity syndrome (IPS). Here, we analyzed the interaction between deletion mutants of FATP4 and RPE6 5 as well as the impacts of IPS‐associated FATP4 mutations on RPE65 expression, 11‐cis‐retinol synthesis, and all‐tran...
Source: FEBS Letters - October 8, 2019 Category: Biochemistry Authors: Songhua Li, John F. Green, Minghao Jin Tags: Research Letter Source Type: research

Stabilization of soluble high ‐affinity T‐cell receptor with de novo disulfide bonds
Soluble T ‐cell receptors (TCRs) have recently gained visibility as target‐recognition units of anticancer immunotherapeutic agents. Here, we improved the thermal stability of the well‐expressed high‐affinity A6 TCR by introducing pairs of cysteines in the invariable parts of the α‐ and β‐chain. A mutant with a novel intradomain disulfide bond in each chain also tested superior to the wild‐type in the accelerated stability assay. Binding of the mutant to the soluble cognate peptide (cp)–MHC and to the peptide‐loaded T2 cell line was equal to the wild‐type A6 TCR. The same stabiliza tion m...
Source: FEBS Letters - October 8, 2019 Category: Biochemistry Authors: Fl ávio Sádio, Gerhard Stadlmayr, Katharina Stadlbauer, Maximilian Gräf, Agnes Scharrer, Florian Rüker, Gordana Wozniak‐Knopp Tags: Research Article Source Type: research

Inactivation of the glutathione peroxidase GPx4 by the ferroptosis ‐inducing molecule RSL3 requires the adaptor protein 14‐3‐3ε
AbstractRas ‐selective lethal small molecule 3 (RSL3), a drug candidate prototype for cancer chemotherapy, triggers ferroptosis by inactivating the glutathione peroxidase GPx4. Here, we report the purification of the protein indispensable for GPx4 inactivation by RSL3. Mass spectrometric analysis identified 1 4‐3‐3 isoforms as candidates, and recombinant human 14‐3‐3ε confirms the identification. The function of 14‐3‐3ε is redox‐regulated. Moreover, overexpression or silencing of the gene coding for 14‐3‐3ε consistently controls the inactivation of GPx4 by RSL3. The interaction o...
Source: FEBS Letters - October 3, 2019 Category: Biochemistry Authors: Ana ‐Marija Vučković, Valentina Bosello Travain, Luciana Bordin, Giorgio Cozza, Giovanni Miotto, Monica Rossetto, Stefano Toppo, Rina Venerando, Mattia Zaccarin, Matilde Maiorino, Fulvio Ursini, Antonella Roveri Tags: Research Articles Source Type: research

Tolrestat acts atypically as a competitive inhibitor of the thermostable aldo ‐keto reductase Tm1743 from Thermotoga maritime
AbstractTolrestat and epalrestat have been characterized as non ‐competitive inhibitors of Aldo‐ketone reductase 1B1 (AKR1B1), a leading drug target for the treatment of Type 2 Diabetes complications. However, clinical applications are limited for most AKR1B1 inhibitors due to adverse effects of cross‐inhibition with other AKRs. Here, we report an atypical competitive binding and inhibitory effect of tolrestat on the thermostable AKR Tm1743 fromThermotoga maritima. Analysis of the Tm1743 crystal structure in complex with tolrestat alone and epalrestat ‐NADP+ shows that tolrestat, but not epalrestat, binding trigger...
Source: FEBS Letters - October 1, 2019 Category: Biochemistry Authors: Chenyun Zhang, Zhenzhen Min, Xuemeng Liu, Chao Wang, Zhiguo Wang, Jiejie Shen, Wanrong Tang, Xin Zhang, Dan Liu, Xiaoling Xu Tags: COMMUNICATION Source Type: research

Diverse roles for CDK ‐associated activity during spermatogenesis
AbstractThe primary function of cyclin ‐dependent kinases (CDKs) in complex with their activating cyclin partners, is to promote mitotic division in somatic cells. This canonical cell cycle‐associated activity is also crucial for fertility as it allows the proliferation and differentiation of stem cells within the reproductive organs to generate meiotically competent cells. Intriguingly several CDKs exhibit meiosis‐specific functions and are essential for the completion of the two reductional meiotic divisions required to generate haploid gametes. These meiosis‐specific functions are mediated by both known CDK/cycl...
Source: FEBS Letters - September 30, 2019 Category: Biochemistry Authors: Nathan Palmer, S. Zakiah A. Talib, Philipp Kaldis Tags: REVIEW Source Type: research

Bistable switches as integrators and actuators during cell cycle progression
AbstractProgression through the cell cycle is driven by bistable switches —specialized molecular circuits that govern transitions from one cellular state to another. Although the mechanics of bistable switches are relatively well understood, it is less clear how cells integrate multiple sources of molecular information to engage these switches. Here, we describe how bis table switches act as hubs of information processing and examine how variability, competition, and inheritance of molecular signals determine the timing of the Rb‐E2F bistable switch that controls cell cycle entry. Bistable switches confer both robu...
Source: FEBS Letters - September 30, 2019 Category: Biochemistry Authors: Wayne Stallaert, Katarzyna M. Kedziora, Hui Xiao Chao, Jeremy E. Purvis Tags: PERSPECTIVE Source Type: research

ATPase reaction cycle of P4 ‐ATPases affects their transport from the endoplasmic reticulum
AbstractP4 ‐ATPases belonging to the P‐type ATPase superfamily mediate active transport of phospholipids across cellular membranes. Most P4‐ATPases, except ATP9A and ATP9B proteins, form heteromeric complexes with CDC50 proteins, which are required for transport of P4‐ATPases from the endoplasmic retic ulum (ER) to their final destinations. P‐type ATPases form auto‐phosphorylated intermediates during the ATPase reaction cycle. However, the association of the catalytic cycle of P4‐ATPases with their transport from the ER and their cellular localization has not been studied. Here, we show that transport of ATP9...
Source: FEBS Letters - September 30, 2019 Category: Biochemistry Authors: Takuya Tone, Kazuhisa Nakayama, Hiroyuki Takatsu, Hye ‐Won Shin Tags: Research Letter Source Type: research

Diverse roles for CDK ‐associated activity during spermatogenesis
AbstractThe primary function of cyclin ‐dependent kinases (CDKs) in complex with their activating cyclin partners, is to promote mitotic division in somatic cells. This canonical cell cycle‐associated activity is also crucial for fertility as it allows the proliferation and differentiation of stem cells within the reproductive organs to generate meiotically competent cells. Intriguingly several CDKs exhibit meiosis‐specific functions and are essential for the completion of the two reductional meiotic divisions required to generate haploid gametes. These meiosis‐specific functions are mediated by both known CDK/cycl...
Source: FEBS Letters - September 30, 2019 Category: Biochemistry Authors: Nathan Palmer, S. Zakiah A. Talib, Philipp Kaldis Tags: REVIEW Source Type: research

Bistable switches as integrators and actuators during cell cycle progression
AbstractProgression through the cell cycle is driven by bistable switches —specialized molecular circuits that govern transitions from one cellular state to another. Although the mechanics of bistable switches are relatively well understood, it is less clear how cells integrate multiple sources of molecular information to engage these switches. Here, we describe how bis table switches act as hubs of information processing and examine how variability, competition, and inheritance of molecular signals determine the timing of the Rb‐E2F bistable switch that controls cell cycle entry. Bistable switches confer both robu...
Source: FEBS Letters - September 30, 2019 Category: Biochemistry Authors: Wayne Stallaert, Katarzyna M. Kedziora, Hui Xiao Chao, Jeremy E. Purvis Tags: PERSPECTIVE Source Type: research

ATPase reaction cycle of P4 ‐ATPases affects their transport from the endoplasmic reticulum
AbstractP4 ‐ATPases belonging to the P‐type ATPase superfamily mediate active transport of phospholipids across cellular membranes. Most P4‐ATPases, except ATP9A and ATP9B proteins, form heteromeric complexes with CDC50 proteins, which are required for transport of P4‐ATPases from the endoplasmic retic ulum (ER) to their final destinations. P‐type ATPases form auto‐phosphorylated intermediates during the ATPase reaction cycle. However, the association of the catalytic cycle of P4‐ATPases with their transport from the ER and their cellular localization has not been studied. Here, we show that transport of ATP9...
Source: FEBS Letters - September 30, 2019 Category: Biochemistry Authors: Takuya Tone, Kazuhisa Nakayama, Hiroyuki Takatsu, Hye ‐Won Shin Tags: Research Letter Source Type: research

2 ‐oxoglutarate modulates the affinity of FurA for the ntcA promoter in Anabaena sp. PCC 7120
This study provides evidence of a new additional control point in the complex network controlled by the NtcA and FurA proteins. (Source: FEBS Letters)
Source: FEBS Letters - September 29, 2019 Category: Biochemistry Authors: Jorge Gu ío, Cristina Sarasa‐Buisan, Adrián Velázquez‐Campoy, María Teresa Bes, María F. Fillat, María Luisa Peleato, Emma Sevilla Tags: Research Letter Source Type: research

Transcriptional downregulation of miR ‐127‐3p by CTCF promotes prostate cancer bone metastasis by targeting PSMB5
AbstractProstate cancer (PCa) is one of the most common cancers in males and particularly tends to metastasize to bone. Currently, metastatic bone disease is incurable, and new therapies need to be developed. Our study aims to determine the role of miR ‐127‐3p in PCa metastasis to bone. The results demonstrate that miR‐127‐3p is markedly reduced in bone metastasis‐positive PCa tissues relative to that in bone metastasis‐negative PCa tissues. Furthermore, overexpressing miR‐127‐3p inhibits PCa cell invasion and migrationin vitro by targeting the proteasome β subunit PSMB5. Moreover, CTCF transcriptional...
Source: FEBS Letters - September 28, 2019 Category: Biochemistry Authors: Jiaxing Fan, Wenzhi Du, Hui Zhang, Yunchao Wang, Kai Li, Yong Meng, Jianning Wang Tags: Research Articles Source Type: research

Ligand ‐dependent intra‐ and inter‐domain motions in the PDZ12 tandem regulate binding interfaces in postsynaptic density protein‐95
AbstractThe postsynaptic density protein ‐95 (PSD‐95) regulates synaptic plasticity through interactions mediated by its peptide binding PDZ domains. The two N‐terminal PDZ domains of PSD‐95 form an autonomous structural unit, and their interdomain orientation and dynamics depend on ligand binding. To understand the mechanistic det ails of the effect of ligand binding, we generated conformational ensembles using available experimentally determined NOE interatomic distances and S2 order parameters. In our approach, the fast dynamics of the two domains is treated independently. We find that intradomain structural cha...
Source: FEBS Letters - September 28, 2019 Category: Biochemistry Authors: Bertalan Kov ács, Nóra Zajácz‐Epresi, Zoltán Gáspári Tags: Research Letter Source Type: research

Cell cycle dynamics in the reprogramming of cellular identity
AbstractReprogramming cellular identity is fundamentally at odds with replication of the genome: cell fate reprogramming requires complex multi ‐dimensional epigenomic changes, whereas genome replication demands fidelity. In this review, we discuss how the pace of genome's replication and cell cycle influences the way daughter cells take on their identity. We highlight several biochemical processes that are pertinent to cell fate control, whose propagation into the daughter cells should be governed by more complex mechanisms than simple templated‐replication. With this mindset, we summarize multiple scenarios where rap...
Source: FEBS Letters - September 28, 2019 Category: Biochemistry Authors: Xiao Hu, Anna E. Eastman, Shangqin Guo Tags: REVIEW Source Type: research

Transcriptional downregulation of miR ‐127‐3p by CTCF promotes prostate cancer bone metastasis by targeting PSMB5
AbstractProstate cancer (PCa) is one of the most common cancers in males and particularly tends to metastasize to bone. Currently, metastatic bone disease is incurable, and new therapies need to be developed. Our study aims to determine the role of miR ‐127‐3p in PCa metastasis to bone. The results demonstrate that miR‐127‐3p is markedly reduced in bone metastasis‐positive PCa tissues relative to that in bone metastasis‐negative PCa tissues. Furthermore, overexpressing miR‐127‐3p inhibits PCa cell invasion and migrationin vitro by targeting the proteasome β subunit PSMB5. Moreover, CTCF transcriptional...
Source: FEBS Letters - September 28, 2019 Category: Biochemistry Authors: Jiaxing Fan, Wenzhi Du, Hui Zhang, Yunchao Wang, Kai Li, Yong Meng, Jianning Wang Tags: Research Articles Source Type: research

Ligand ‐dependent intra‐ and inter‐domain motions in the PDZ12 tandem regulate binding interfaces in postsynaptic density protein‐95
AbstractThe postsynaptic density protein ‐95 (PSD‐95) regulates synaptic plasticity through interactions mediated by its peptide binding PDZ domains. The two N‐terminal PDZ domains of PSD‐95 form an autonomous structural unit, and their interdomain orientation and dynamics depend on ligand binding. To understand the mechanistic det ails of the effect of ligand binding, we generated conformational ensembles using available experimentally determined NOE interatomic distances and S2 order parameters. In our approach, the fast dynamics of the two domains is treated independently. We find that intradomain structural cha...
Source: FEBS Letters - September 28, 2019 Category: Biochemistry Authors: Bertalan Kov ács, Nóra Zajácz‐Epresi, Zoltán Gáspári Tags: Research Letter Source Type: research

Cell cycle dynamics in the reprogramming of cellular identity
AbstractReprogramming cellular identity is fundamentally at odds with replication of the genome: cell fate reprogramming requires complex multi ‐dimensional epigenomic changes, whereas genome replication demands fidelity. In this review, we discuss how the pace of genome's replication and cell cycle influences the way daughter cells take on their identity. We highlight several biochemical processes that are pertinent to cell fate control, whose propagation into the daughter cells should be governed by more complex mechanisms than simple templated‐replication. With this mindset, we summarize multiple scenarios where rap...
Source: FEBS Letters - September 28, 2019 Category: Biochemistry Authors: Xiao Hu, Anna E. Eastman, Shangqin Guo Tags: REVIEW Source Type: research

Single ‐cell RNA sequencing reveals chemokine self‐feeding of myeloma cells promotes extramedullary metastasis
In this study, we aimed to determine the mechanisms underlying the initial extramedullary translocation of myeloma cells from bone marrow into peripheral blood. We find that clonal circulating plasma cells (cPCs) are more frequently detected by flowcytometry in  extramedullary plasmacytoma (EMP) patients and worsens their prognosis. It is technically much easier to collect single cPCs using FACS than it is to perform EMP biopsy. Therefore, combining EMP imaging with cPC detection may be a promising strategy for prognostic stratification. Here, using single‐cell transcriptome analysis, we fin...
Source: FEBS Letters - September 27, 2019 Category: Biochemistry Authors: Shuang Geng, Jing Wang, Zhang Xiannian, Jia ‐jia Zhang, Fan Wu, Yuhong Pang, Yuping Zhong, Jianbin Wang, Wenming Wang, Xiaoqing Lyu, Yanyi Huang, Hongmei Jing Tags: RESEARCH ARTICLES Source Type: research

Jim's View: Is the Golgi stack a phase ‐separated liquid crystal?
FEBS Letters, EarlyView. (Source: FEBS Letters)
Source: FEBS Letters - September 27, 2019 Category: Biochemistry Authors: James E. Rothman Tags: The Scientists ’ Forum Source Type: research