Kasuno, K. and Naqvi, A. and DeRicco, J. and Yamamori, T. and Santhanam, L. and Mattagajasingh, I. and Yang, S. and Meyskens, F. L. and Bosserhoff, A.-K and Irani, K. (2007) Antagonism of p66shc by melanoma inhibitory activity. CELL DEATH AND DIFFERENTIATION, 14 (8). pp. 1414-1421. ISSN 1350-9047,
Full text not available from this repository. (Request a copy)Abstract
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 (H2O2), and inhibits basal and H2O2-induced phosphorylation of p66shc on serine 36 and H2O2-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 H2O2 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MALIGNANT-MELANOMA; OXIDATIVE STRESS; SIGNALING PATHWAY; ADAPTER PROTEIN; GENE-EXPRESSION; SERUM MARKER; CELLS; MIA; APOPTOSIS; PROGRESSION; melanoma; p66shc; oxidative stress |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Dec 2020 06:57 |
| Last Modified: | 02 Dec 2020 06:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32422 |
Actions (login required)
 |
View Item |
