Antagonism of p66shc by melanoma inhibitory activity

K Kasuno; A Naqvi; J Dericco; T Yamamori; L Santhanam; I Mattagajasingh; S Yang; F L Meyskens; A-K Bosserhoff; K Irani

doi:10.1038/sj.cdd.4402131

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Antagonism of p66shc by melanoma inhibitory activity

Journal article

Open access

Peer reviewed

Antagonism of p66shc by melanoma inhibitory activity

K Kasuno, A Naqvi, J Dericco, T Yamamori, L Santhanam, I Mattagajasingh, S Yang, F L Meyskens, A-K Bosserhoff and K Irani

Cell death and differentiation, Vol.14(8), pp.1414-1421

08/2007

DOI: 10.1038/sj.cdd.4402131

PMID: 17431427

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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 (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.

Phosphorylation

Oxidative Stress

Apoptosis

Adaptor Proteins, Signal Transducing - chemistry

Melanoma - metabolism

Extracellular Matrix Proteins - genetics

Humans

Cercopithecus aethiops

Melanoma - pathology

Neoplasm Proteins - metabolism

Hydrogen Peroxide - metabolism

Animals

Src Homology 2 Domain-Containing, Transforming Protein 1

Adaptor Proteins, Signal Transducing - antagonists & inhibitors

Melanoma - genetics

Cell Line, Tumor

Protein Binding

Mice

Adaptor Proteins, Signal Transducing - metabolism

Neoplasm Proteins - genetics

Binding Sites

COS Cells

Extracellular Matrix Proteins - metabolism

Shc Signaling Adaptor Proteins

Details

Title: Subtitle: Antagonism of p66shc by melanoma inhibitory activity
Creators: K Kasuno - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
A Naqvi
J Dericco
T Yamamori
L Santhanam
I Mattagajasingh
S Yang
F L Meyskens
A-K Bosserhoff
K Irani
Resource Type: Journal article
Publication Details: Cell death and differentiation, Vol.14(8), pp.1414-1421
DOI: 10.1038/sj.cdd.4402131
PMID: 17431427
NLM abbreviation: Cell Death Differ
ISSN: 1350-9047
eISSN: 1476-5403
Publisher: England
Language: English
Date published: 08/2007
Academic Unit: Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984047652802771

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