NAD(P)H quinone oxidoreductase 1 inhibits the proteasomal degradation of the tumour suppressor p33ING1b

The tumour suppressor p33 ING1b ( ING1b for inhibitor of growth family, member 1b) is important in cellular stress responses, including cell‐cycle arrest, apoptosis, chromatin remodelling and DNA repair; however, its degradation pathway is still unknown. Recently, we showed that genotoxic stress ind...

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Bibliographic Details
Published in:EMBO reports 2008-06, Vol.9 (6), p.576-581
Main Authors: Garate, Marco, Wong, Ronald P C, Campos, Eric I, Wang, Yemin, Li, Gang
Format: Article
Language:English
Subjects:
Cancer
Degradation
Deoxyribonucleic acid
DNA
EMBO31
Inhibitor drugs
Irradiation
Molecular biology
NQO1
phosphorylation
proteasome
protein degradation
Scientific Report
Stress
Tumors
tumour suppressor p33ING1b
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Summary:The tumour suppressor p33 ING1b ( ING1b for inhibitor of growth family, member 1b) is important in cellular stress responses, including cell‐cycle arrest, apoptosis, chromatin remodelling and DNA repair; however, its degradation pathway is still unknown. Recently, we showed that genotoxic stress induces p33 ING1b phosphorylation at Ser 126, and abolishment of Ser 126 phosphorylation markedly shortened its half‐life. Therefore, we suggest that Ser 126 phosphorylation modulates the interaction of p33 ING1b with its degradation machinery, stabilizing this protein. Combining the use of inhibitors of the main degradation pathways in the nucleus (proteasome and calpains), partial isolation of the proteasome complex, and in vitro interaction and degradation assays, we set out to determine the degradation mechanism of p33 ING1b . We found that p33 ING1b is degraded in the 20S proteasome and that NAD(P)H quinone oxidoreductase 1 (NQO1), an oxidoreductase previously shown to modulate the degradation of p53 in the 20S proteasome, inhibits the degradation of p33 ING1b . Furthermore, ultraviolet irradiation induces p33 ING1b phosphorylation at Ser 126, which, in turn, facilitates its interaction with NQO1.
ISSN:1469-221X
1469-3178
DOI:10.1038/embor.2008.48