Cytoplasmic CUL9/PARC ubiquitin ligase is a tumor suppressor and promotes p53-dependent apoptosis

Xin-Hai Pei, Feng Bai, Zhijun Li, Matthew D. Smith, Gabrielle Whitewolf, Ran Jin, Yue Xiong

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

A wide range of cell stresses, including DNA damage, signal to p53 through posttranslational modification of p53. The cytoplasmic functions of p53 are emerging as an important constituent of role of p53 in tumor suppression. Here, we report that deletion of the Cul9 (formerly Parc) gene, which encodes an E3 ubiquitin ligase that binds to p53 and localizes in the cytoplasm, resulted in spontaneous tumor development, accelerated Em-Myc-induced lymphomagenesis, and rendered mice susceptible to carcinogenesis. Cul9-p53 double-mutant mice exhibited indistinguishable tumor phenotypes as p53 single-mutant mice, indicating that the function of Cul9 in tumor suppression is largely mediated by p53. Deletion of Cul9 had no significant effect on cell-cycle progression, but attenuated DNA damage-induced apoptosis. Ectopic expression of wild-type CUL9, but not a point mutant CUL9 deficient in p53 binding, promotes apoptosis. These results show CUL9 as a potential p53-activating E3 ligase in the cytoplasm.

Original languageEnglish
Pages (from-to)2969-2977
Number of pages9
JournalCancer Research
Volume71
Issue number8
DOIs
StatePublished - Apr 15 2011
Externally publishedYes

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Ligases
Ubiquitin
Apoptosis
Ubiquitin-Protein Ligases
DNA Damage
Neoplasms
Cytoplasm
Post Translational Protein Processing
Cell Cycle
Carcinogenesis
Phenotype
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cytoplasmic CUL9/PARC ubiquitin ligase is a tumor suppressor and promotes p53-dependent apoptosis. / Pei, Xin-Hai; Bai, Feng; Li, Zhijun; Smith, Matthew D.; Whitewolf, Gabrielle; Jin, Ran; Xiong, Yue.

In: Cancer Research, Vol. 71, No. 8, 15.04.2011, p. 2969-2977.

Research output: Contribution to journalArticle

Pei, Xin-Hai ; Bai, Feng ; Li, Zhijun ; Smith, Matthew D. ; Whitewolf, Gabrielle ; Jin, Ran ; Xiong, Yue. / Cytoplasmic CUL9/PARC ubiquitin ligase is a tumor suppressor and promotes p53-dependent apoptosis. In: Cancer Research. 2011 ; Vol. 71, No. 8. pp. 2969-2977.
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