SOCS1 links cytokine signaling to p53 and senescence
| Autor: | Sheela Ramanathan, Xavier Deschênes-Simard, Viviane Calabrese, Gerardo Ferbeyre, Frédérick A. Mallette, Adrian Moores, Julien Gagnon, Subburaj Ilangumaran |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Senescence
DNA damage Cell Cycle Proteins Suppressor of Cytokine Signaling Proteins Ataxia Telangiectasia Mutated Proteins Biology Protein Serine-Threonine Kinases Transactivation Mice Suppressor of Cytokine Signaling 1 Protein Cell Line Tumor STAT5 Transcription Factor Animals Humans Phosphorylation Molecular Biology Cellular Senescence Cell Nucleus Suppressor of cytokine signaling 1 Tumor Suppressor Proteins Cell Biology Cell cycle Cell biology DNA-Binding Proteins Cancer research RNA Interference Signal transduction Tumor Suppressor Protein p53 DNA Damage Signal Transduction |
| Zdroj: | Molecular cell. 36(5) |
| ISSN: | 1097-4164 |
| Popis: | SOCS1 is lost in many human tumors, but its tumor suppression activities are not well understood. We report that SOCS1 is required for transcriptional activity, DNA binding, and serine 15 phosphorylation of p53 in the context of STAT5 signaling. In agreement, inactivation of SOCS1 disabled p53-dependent senescence in response to oncogenic STAT5A and radiation-induced apoptosis in T cells. In addition, SOCS1 was sufficient to induce p53-dependent senescence in fibroblasts. The mechanism of activation of p53 by SOCS1 involved a direct interaction between the SH2 domain of SOCS1 and the N-terminal transactivation domain of p53, while the C-terminal domain of SOCS1 containing the SOCS Box mediated interaction with the DNA damage-regulated kinases ATM/ATR. Also, SOCS1 colocalized with ATM at DNA damage foci induced by oncogenic STAT5A. Collectively, these results add another component to the p53 and DNA damage networks and reveal a mechanism by which SOCS1 functions as a tumor suppressor. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|