| First Author | Kasuno K | Year | 2007 |
| Journal | Cell Death Differ | Volume | 14 |
| Issue | 8 | Pages | 1414-21 |
| PubMed ID | 17431427 | Mgi Jnum | J:139292 |
| Mgi Id | MGI:3807715 | Doi | 10.1038/sj.cdd.4402131 |
| Citation | Kasuno K, et al. (2007) Antagonism of p66shc by melanoma inhibitory activity. Cell Death Differ 14(8):1414-21 |
| abstractText | The p66shc protein governs oxidant stress and mammalian lifespan. Here, we identify melanoma inhibitory activity (MIA), a protein secreted by melanoma cells, as a novel binding partner and antagonist of p66shc. The N-terminal collagen homology-2 (CH2) domain of p66shc binds to the Src Homology-3 (SH3)-like domain of MIA in vitro. In cells, ectopically expressed MIA and p66shc colocalize and co-precipitate. MIA also co-precipitates with the CH2 domain of p66shc in vivo. MIA expression in vivo suppresses p66shc-stimulated increase in endogenous hydrogen peroxide (H(2)O(2)), and inhibits basal and H(2)O(2)-induced phosphorylation of p66shc on serine 36 and H(2)O(2)-induced death. In human melanoma cells expressing MIA, endogenous MIA and p66shc co-precipitate. Downregulation of MIA in melanoma cells increases basal and ultraviolet radiation (UVR)-induced phosphorylation of p66shc on serine 36, augments endogenous H(2)O(2) levels, and increases their susceptibility to UVR-induced death. These findings show that MIA binds to p66shc, and suggest that this interaction antagonizes phosphorylation and function of p66shc. |
