Inhibition of stress-inducible kinase pathways by tumorigenic mutant p53

Yoichi Ohiro, Anny Usheva, Shinichiro Kobayashi, Shannon L. Duffy, Regan Nantz, David Gius, Nobuo Horikoshi*

*Corresponding author for this work

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

More than 50% of human cancers contain p53 gene mutations and as a result accumulate altered forms of the full-length p53 protein. Although certain tumor types expressing mutant p53 protein have a poor prognostic process, the precise role of mutant p53 protein in highly malignant tumor cells is not well defined. Some p53 mutants, but not wild-type p53, are shown here to interact with Daxx, a Fas-binding protein that activates stress-inducible kinase pathways. Interaction of Daxx with p53 is highly dependent upon the specific mutation of p53. Tumorigenic mutants of p53 bind to Daxx and inhibit Daxx-dependent activation of the apoptosis signal-regulating kinase 1 stress-inducible kinases and Jun NH2-terminal kinase. Mutant p53 forms complexes with Daxx in cells, and consequently, mutant p53 is able to rescue cells from Daxx-dependent inhibition of proliferation. Thus, the accumulation of mutant p53 in tumor cells may contribute to tumorigenesis by inhibiting stress-inducible kinase pathways.

Original languageEnglish (US)
Pages (from-to)322-334
Number of pages13
JournalMolecular and cellular biology
Volume23
Issue number1
DOIs
StatePublished - Jan 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Ohiro, Y., Usheva, A., Kobayashi, S., Duffy, S. L., Nantz, R., Gius, D., & Horikoshi, N. (2003). Inhibition of stress-inducible kinase pathways by tumorigenic mutant p53. Molecular and cellular biology, 23(1), 322-334. https://doi.org/10.1128/MCB.23.1.322-334.2003