CUL9 Mediates the Functions of the 3M Complex and Ubiquitylates Survivin to Maintain Genome Integrity

Zhijun Li, Xin-Hai Pei, Jun Yan, Feng Yan, Kathryn M. Cappell, Angelique W. Whitehurst, Yue Xiong

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The Cullin 9 (CUL9) gene encodes a putative E3 ligase that localizes in the cytoplasm. Cul9 null mice develop spontaneous tumors in multiple organs; however, both the cellular and the molecular mechanisms of CUL9 in tumor suppression are currently unknown. We show here that deletion of Cul9 leads to abnormal nuclear morphology, increased DNA damage, and aneuploidy. CUL9 knockdown rescues the microtubule and mitosis defects in cells depleted for CUL7 or OBSL1, two genes that are mutated in a mutually exclusive manner in 3M growth retardation syndrome and function in microtubule dynamics. CUL9 promotes the ubiquitylation and degradation of survivin and is inhibited by CUL7. Depletion of CUL7 decreases survivin level, and overexpression of survivin rescues the defects caused by CUL7 depletion. We propose a 3M-CUL9-survivin pathway in maintaining microtubule and genome integrity, normal development, and tumor suppression.

Original languageEnglish
Pages (from-to)805-819
Number of pages15
JournalMolecular Cell
Volume54
Issue number5
DOIs
StatePublished - Jun 5 2014

Fingerprint

Cullin Proteins
Genome
Microtubules
Neoplasms
Ubiquitin-Protein Ligases
Ubiquitination
Aneuploidy
Mitosis
Genes
DNA Damage
Cytoplasm
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

CUL9 Mediates the Functions of the 3M Complex and Ubiquitylates Survivin to Maintain Genome Integrity. / Li, Zhijun; Pei, Xin-Hai; Yan, Jun; Yan, Feng; Cappell, Kathryn M.; Whitehurst, Angelique W.; Xiong, Yue.

In: Molecular Cell, Vol. 54, No. 5, 05.06.2014, p. 805-819.

Research output: Contribution to journalArticle

Li, Zhijun ; Pei, Xin-Hai ; Yan, Jun ; Yan, Feng ; Cappell, Kathryn M. ; Whitehurst, Angelique W. ; Xiong, Yue. / CUL9 Mediates the Functions of the 3M Complex and Ubiquitylates Survivin to Maintain Genome Integrity. In: Molecular Cell. 2014 ; Vol. 54, No. 5. pp. 805-819.
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