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Genome-wide siRNA screening reveals that DCAF4-mediated ubiquitination of optineurin stimulates autophagic degradation of Cu,Zn-superoxide dismutase Cell Biology
Cu, Zn superoxide dismutase (SOD1) is one of the genes implicated in the devastating neurodegenerative disorder amyotrophic lateral sclerosis (ALS). Although the precise mechanisms of SOD1 mutant (SOD1mut)-induced motoneuron toxicity are still unclear, defects in SOD1 proteostasis are known to have a critical role in ALS pathogenesis. We previously reported that the SOD1mut adopts a conformation that exposes a Derlin-1–binding region (DBR) and that DBR-exposed SOD1 interacts with Derlin-1, leading to motoneuron death. We also found that an environmental change, i.e. zinc depletion, induces a conformational change in WT S...
Source: Journal of Biological Chemistry - March 5, 2020 Category: Chemistry Authors: Kengo Homma, Hiromitsu Takahashi, Naomi Tsuburaya, Isao Naguro, Takao Fujisawa, Hidenori Ichijo Tags: Molecular Bases of Disease Source Type: research

Fibroblast growth factor 2 induces proliferation and fibrosis via SNAI1-mediated activation of CDK2 and ZEB1 in corneal endothelium Signal Transduction
Investigating stimulation of endogenous wound healing in corneal endothelial cells (CECs) may help address the global shortage of donor corneas by decreasing the number of transplants performed for blindness because of endothelial dysfunction. We previously reported that IL-1β stimulation leads to fibroblast growth factor (FGF2) expression, enhancing migration and proliferation of mammalian CECs. However, FGF2 also promotes the endothelial-mesenchymal transition, which can lead to retrocorneal membrane formation and blindness. This prompted us to investigate downstream FGF2 signaling targets that could be manipulated to p...
Source: Journal of Biological Chemistry - March 9, 2018 Category: Chemistry Authors: Jeong Goo Lee, Eric Jung, Martin Heur Tags: Cell Biology Source Type: research

Palmitoylation of caveolin-1 is regulated by the same DHHC acyltransferases that modify steroid hormone receptors Neurobiology
Palmitoylation is a reversible post-translational addition of a 16-carbon lipid chain involved in trafficking and compartmentalizing target proteins. It is important for many cellular functions, including signaling via membrane-localized estrogen receptors (ERs). Within the nervous system, palmitoylation of ERα is necessary for membrane surface localization and mediation of downstream signaling through the activation of metabotropic glutamate receptors (mGluRs). Substitution of the single palmitoylation site on ERα prevents its physical association with the integral membrane protein caveolin-1 (CAV1), required for the fo...
Source: Journal of Biological Chemistry - October 12, 2018 Category: Chemistry Authors: Katherine R. Tonn Eisinger, Kevin M. Woolfrey, Samuel P. Swanson, Stephen A. Schnell, John Meitzen, Mark Dell'Acqua, Paul G. Mermelstein Tags: Cell Biology Source Type: research

Molecules, Vol. 28, Pages 5934: Caspase-1 Regulates the Apoptosis and Pyroptosis Induced by Phthalocyanine Zinc-Mediated Photodynamic Therapy in Breast Cancer MCF-7 Cells
o Chunhui Xia Photodynamic therapy (PDT) is an innovative and perspective antineoplastic therapy. Tetra-α-(4-carboxyphenoxy) phthalocyanine zinc (TαPcZn)-mediated PDT (TαPcZn-PDT) has shown antitumor activity in some tumor cells, but the manner in which caspase-1 is involved in the regulation of apoptosis and pyroptosis in the TαPcZn-PDT-treated breast cancer MCF-7 cells is unclear. Therefore, effects of TαPcZn-PDT on cytotoxicity, cell viability, apoptosis, pyroptosis, cellular reactive oxygen species (ROS), mitochondrial membrane potential (&...
Source: Molecules - August 8, 2023 Category: Chemistry Authors: Chunjie Ma Yu Wang Wei Chen Ting Hou Honglian Zhang Hongguang Zhang Xu Yao Chunhui Xia Tags: Article Source Type: research

The transcriptional repressor GATAD2B mediates progesterone receptor suppression of myometrial contractile gene expression Gene Regulation
The mechanisms whereby progesterone (P4), acting via the progesterone receptor (PR), inhibits proinflammatory/contractile gene expression during pregnancy are incompletely defined. Using immortalized human myometrial (hTERT-HM) cells stably expressing wild-type PR-A or PR-B (PRWT), we found that P4 significantly inhibited IL-1β induction of the NF-κB target genes, COX-2 and IL-8. P4–PRWT transrepression occurred at the level of transcription initiation and was mediated by decreased recruitment of NF-κB p65 and RNA polymerase II to COX-2 and IL-8 promoters. However, in cells stably expressing a PR-A or PR-B DNA-binding...
Source: Journal of Biological Chemistry - July 28, 2017 Category: Chemistry Authors: Chien-Cheng Chen, Alina P. Montalbano, Imran Hussain, Wan-Ru Lee, Carole R. Mendelson Tags: Gene Regulation Source Type: research

The palmitoyltransferase ZDHHC20 enhances interferon-induced transmembrane protein 3 (IFITM3) palmitoylation and antiviral activity Microbiology
Interferon-induced transmembrane protein 3 (IFITM3) is a cellular endosome- and lysosome-localized protein that restricts numerous virus infections. IFITM3 is activated by palmitoylation, a lipid posttranslational modification. Palmitoylation of proteins is primarily mediated by zinc finger DHHC domain–containing palmitoyltransferases (ZDHHCs), but which members of this enzyme family can modify IFITM3 is not known. Here, we screened a library of human cell lines individually lacking ZDHHCs 1–24 and found that IFITM3 palmitoylation and its inhibition of influenza virus infection remained strong in the absence of any sin...
Source: Journal of Biological Chemistry - December 29, 2017 Category: Chemistry Authors: Temet M. McMichael, Lizhi Zhang, Mahesh Chemudupati, Jocelyn C. Hach, Adam D. Kenney, Howard C. Hang, Jacob S. Yount Tags: Immunology Source Type: research

Kruppel-like factor 10 (KLF10) is transactivated by the transcription factor C/EBP{beta} and involved in early 3T3-L1 preadipocyte differentiation Gene Regulation
Adipose tissue stores energy and plays an important role in energy homeostasis. CCAAT/enhancer-binding protein β (C/EBPβ) is an important early transcription factor for 3T3-L1 preadipocyte differentiation, facilitating mitotic clonal expansion (MCE) and transactivating C/EBPα and peroxisome proliferator–activated receptor-γ (PPARγ) to promote adipogenesis. C/EBPβ is induced early, but the expression of antimitotic C/EBPα and PPARγ is not induced until ∼48 h. The delayed expression of C/EBPα and PPARγ is thought to ensure MCE progression, but the molecular mechanism for this delay remains elusive. Here, we sho...
Source: Journal of Biological Chemistry - September 7, 2018 Category: Chemistry Authors: Yuan Liu, Wan-Qiu Peng, Ying-Ying Guo, Yang Liu, Qi-Qun Tang, Liang Guo Tags: Cell Biology Source Type: research

The extracellular sulfatase SULF2 promotes liver tumorigenesis by stimulating assembly of a promoter-looping GLI1-STAT3 transcriptional complex Cell Biology
The expression of the extracellular sulfatase SULF2 has been associated with increased hepatocellular carcinoma (HCC) growth and poor patient survival. However, the molecular mechanisms underlying SULF2-associated tumor growth remain unclear. To address this gap, here we developed a transgenic mouse overexpressing Sulf2 in hepatocytes under the control of the transthyretin promoter. In this model, Sulf2 overexpression potentiated diethylnitrosamine-induced HCC. Further analysis indicated that the transcription factor GLI family zinc finger 1 (GLI1) mediates Sulf2 expression during HCC development. A cross of the Sulf2-over...
Source: Journal of Biological Chemistry - February 27, 2020 Category: Chemistry Authors: Ryan M. Carr, Paola A. Romecin Duran, Ezequiel J. Tolosa, Chenchao Ma, Abdul M. Oseini, Catherine D. Moser, Bubu A. Banini, Jianbo Huang, Faizal Asumda, Renumathy Dhanasekaran, Rondell P. Graham, Merih D. Toruner, Stephanie L. Safgren, Luciana L. Almada, Tags: Molecular Bases of Disease Source Type: research