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

56 Citations (Scopus)

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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Dimerization
Ligases
Ubiquitin
Inhibitor of Apoptosis Proteins
Caspase Inhibitors
Ubiquitination
Carcinogenesis
Ubiquitin-Protein Ligases
Oncogenes
Cell Proliferation
Myc associated factor X
Neoplasms
Proteins

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Molecular Biology

Cite this

c-IAP1 Cooperates with Myc by Acting as a Ubiquitin Ligase for Mad1. / Xu, Lei; Zhu, Jidong; Hu, Xiaofang; Zhu, Hong; Kim, Hyoung Tae; LaBaer, Joshua; Goldberg, Alfred; Yuan, Junying.

In: Molecular Cell, Vol. 28, No. 5, 14.12.2007, p. 914-922.

Research output: Contribution to journalArticle

Xu, L, Zhu, J, Hu, X, Zhu, H, Kim, HT, LaBaer, J, Goldberg, A & Yuan, J 2007, 'c-IAP1 Cooperates with Myc by Acting as a Ubiquitin Ligase for Mad1', Molecular Cell, vol. 28, no. 5, pp. 914-922. https://doi.org/10.1016/j.molcel.2007.10.027
Xu, Lei ; Zhu, Jidong ; Hu, Xiaofang ; Zhu, Hong ; Kim, Hyoung Tae ; LaBaer, Joshua ; Goldberg, Alfred ; Yuan, Junying. / c-IAP1 Cooperates with Myc by Acting as a Ubiquitin Ligase for Mad1. In: Molecular Cell. 2007 ; Vol. 28, No. 5. pp. 914-922.
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AU - LaBaer, Joshua

AU - Goldberg, Alfred

AU - Yuan, Junying

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