Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
H2AX safeguards genomic stability in a dose-dependent manner; however, mechanisms governing its proteostasis are poorly understood. Here, we identify a PRMT5-RNF168-SMURF2 cascade that regulates H2AX proteostasis. We show that PRMT5 sustains the expression of RNF168, an E3 ubiquitin ligase essential for DNA damage response (DDR). Suppression of PRMT5 occurs in methylthioadenosine phosphorylase (MTAP)-deficient glioblastoma cells and attenuates the expression of RNF168, leading to destabilization of H2AX by E3 ubiquitin ligase SMURF2. RNF168 and SMURF2 serve as a stabilizer and destabilizer of H2AX, respectively, via their dynamic interactions with H2AX. In supporting an important role of this signaling cascade in regulating H2AX, MTAP-deficient glioblastoma cells display higher levels of DNA damage spontaneously or in response to genotoxic agents. These findings reveal a regulatory mechanism of H2AX proteostasis and define a signaling cascade that is essential to DDR and that is disrupted by the loss of a metabolic enzyme in tumor cells.
Pubmed ID: 31533041
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Platform for exploring the anatomic and genetic basis of glioblastoma at the cellular and molecular levels that includes two interactive databases linked together by de-identified tumor specimen numbers to facilitate comparisons across data modalities: * The open public image database, here, providing in situ hybridization data mapping gene expression across the anatomic structures inherent in glioblastoma, as well as associated histological data suitable for neuropathological examination * A companion database (Ivy GAP Clinical and Genomic Database) offering detailed clinical, genomic, and expression array data sets that are designed to elucidate the pathways involved in glioblastoma development and progression. This database requires registration for access. The hope is that researchers all over the world will mine these data and identify trends, correlations, and interesting leads for further studies with significant translational and clinical outcomes. The Ivy Glioblastoma Atlas Project is a collaborative partnership between the Ben and Catherine Ivy Foundation, the Allen Institute for Brain Science and the Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment.
View all literature mentionsSoftware tool as fully automated protein structure homology modeling server, accessible via ExPASy web server, or from program DeepView Swiss Pdb-Viewer. Structural bioinformatics web-server dedicated to homology modeling of 3D protein structures. Used to make protein modelling accessible to all biochemists and molecular biologists.
View all literature mentionsThis monoclonal targets NEDD4
View all literature mentionsThis unknown targets PRMT5
View all literature mentionsThis monoclonal targets alpha-Tubulin (DM1A) Mouse mAb
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets gamma H2A.X (phospho S139)
View all literature mentionsThis monoclonal targets Rnf168
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis monoclonal targets Myc-Tag
View all literature mentionsThis polyclonal targets Ubiquitin
View all literature mentionsThis monoclonal targets Histone H2A.X (D17A3) XP Rabbit mAb
View all literature mentionsThis monoclonal targets SMURF2
View all literature mentionsThis monoclonal targets beta-actin
View all literature mentionsThis polyclonal targets Histone H4 (symmetric di methyl R3) antibody - ChIP Grade
View all literature mentionsThis monoclonal targets K63-linkage Specific Polyubiquitin (D7A11) Rabbit mAb
View all literature mentionsThis unknown targets WWP1
View all literature mentionsThis monoclonal targets p53 (1C12) Mouse mAb
View all literature mentionsThis polyclonal targets Histone H2A.X
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis monoclonal targets Myc Tag
View all literature mentions