c-IAP1 Cooperates with Myc by Acting as a Ubiquitin Ligase for Mad1

Lei Xu, Jidong Zhu, Xiaofang Hu, Hong Zhu, Hyoung Tae Kim, Joshua LaBaer, Alfred Goldberg, Junying Yuan

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

c-IAP1, a member of the inhibitor of apoptosis protein (IAP) family and a RING finger ubiquitin ligase (E3), has been proposed to be an important oncogene. In many types of cancers, the levels of c-IAP1 are upregulated, which contributes positively to tumorigenesis. However, the mechanism by which c-IAP1 promotes tumorigenesis has proven elusive. Although proteins in the IAP family may function as caspase inhibitors, c-IAP1 was shown to be a poor inhibitor of caspases. Here we show that c-IAP1 catalyzes ubiquitination of Max-dimerization protein-1 (Mad1), a cellular antagonist of Myc. Ubiquitination of Mad1 by c-IAP1 accelerates its degradation by the 26S proteasome pathway, and this reduction of the Mad1 levels cooperates with Myc to promote cell proliferation. Our results demonstrate that c-IAP1 exerts its oncogenic functions by promoting the degradation of an important negative regulator in the Myc pathway.

Original languageEnglish (US)
Pages (from-to)914-922
Number of pages9
JournalMolecular Cell
Volume28
Issue number5
DOIs
StatePublished - Dec 14 2007
Externally publishedYes

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Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Xu, L., Zhu, J., Hu, X., Zhu, H., Kim, H. T., LaBaer, J., Goldberg, A., & Yuan, J. (2007). c-IAP1 Cooperates with Myc by Acting as a Ubiquitin Ligase for Mad1. Molecular Cell, 28(5), 914-922. https://doi.org/10.1016/j.molcel.2007.10.027