CUL7 promotes cancer cell survival through promoting Caspase-8 ubiquitination

Int J Cancer. 2019 Sep 1;145(5):1371-1381. doi: 10.1002/ijc.32239. Epub 2019 Mar 18.

Abstract

The Cullin 7 (CUL7) gene encodes a member of the cullin family of E3 ubiquitin ligases. Accumulated evidence suggests that CUL7 is oncogenic. However, the mechanism by which CUL7 improves cancer cell survival has not been fully elucidated. Here, we reported that CUL7 confers anti-apoptotic functions by interacting with Caspase-8. CUL7 prevents Caspase-8 activation by promoting Caspase-8 modification with non-degradative polyubiquitin chains at K215. CUL7 knockdown sensitized cancer cells to TRAIL-induced apoptosis in vitro and in nude mice. These results suggest that CUL7 limits extrinsic apoptotic signaling by promoting Caspase-8 ubiquitination.

Keywords: CUL7; Caspase-8; apoptosis; ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Caspase 8 / metabolism*
  • Cell Line, Tumor
  • Cell Survival / immunology
  • Cullin Proteins / genetics
  • Cullin Proteins / metabolism*
  • Female
  • HEK293 Cells
  • HeLa Cells
  • Heterografts
  • Humans
  • MCF-7 Cells
  • Mice
  • Recombinant Proteins / pharmacology
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology
  • Ubiquitination
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / enzymology*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology

Substances

  • CUL7 protein, human
  • Cullin Proteins
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • CASP8 protein, human
  • Caspase 8