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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zullow, Hayley Shabanowitz, Jeffrey Bernstein, Emily Hunt, Donald F. Peters, Gordon Gil, Jesus Balsbaugh, Jeremy L. Georgilis, Athena Wu, Hsan-au Chandler, Hollie |
| Description | Author Affiliation: Wu HA ( From the Department of Oncological Sciences and.) |
| Abstract | Cbx7 is one of five mammalian orthologs of the Drosophila Polycomb. Cbx7 recognizes methylated lysine residues on the histone H3 tail and contributes to gene silencing in the context of the Polycomb repressive complex 1 (PRC1). However, our knowledge of Cbx7 post-translational modifications remains limited. Through combined biochemical and mass spectrometry approaches, we report a novel phosphorylation site on mouse Cbx7 at residue Thr-118 (Cbx7T118ph), near the highly conserved Polycomb box. The generation of a site-specific antibody to Cbx7T118ph demonstrates that Cbx7 is phosphorylated via MAPK signaling. Furthermore, we find Cbx7T118 phosphorylation in murine mammary carcinoma cells, which can be blocked by MEK inhibitors. Upon EGF stimulation, Cbx7 interacts robustly with other members of PRC1. To test the role of Cbx7T118 phosphorylation in gene silencing, we employed a RAS-induced senescence model system. We demonstrate that Cbx7T118 phosphorylation moderately enhances repression of its target gene p16. In summary, we have identified and characterized a novel MAPK-mediated phosphorylation site on Cbx7 and propose that mitogen signaling to the chromatin template regulates PRC1 function. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 51 |
| Volume Number | 288 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2013-12-20 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | MAP Kinase Signaling System Polycomb Repressive Complex 1 Metabolism Amino Acid Sequence Animals Cell Aging Cell Line, Tumor Chromatin Cyclin-Dependent Kinase Inhibitor P16 Genetics Gene Silencing HEK293 Cells Mice Molecular Sequence Data Mutation Phosphorylation Chemistry Protein Binding Protein Structure, Tertiary Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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