SPSB1 enhances ovarian cancer cell survival by destabilizing p21

Biochem Biophys Res Commun. 2019 Mar 12;510(3):364-369. doi: 10.1016/j.bbrc.2019.01.088. Epub 2019 Jan 31.

Abstract

SPRY domain-containing SOCS box protein 1 (SPSB1) is an E3 ligase adaptor protein with unknown functions in cancer cells. In this study, we found that SPSB1 knockdown markedly decreased the viability and migration of ovarian cancer cells, while ectopic SPSB1 overexpression in IL-3-dependent Ba/F3 cells significantly increased their proliferation rate compared with empty vector-transfected cells. SPSB1 knockdown significantly elevated p21 protein and mRNA levels and induced apoptosis in ovarian cancer cells, as evidenced by increased levels of cleaved PARP and decreased levels of Bcl-2. Notably, mechanistic investigations revealed that SPSB1 accelerated p21 destabilization by directly interacting with p21 and promoting its ubiquitin-mediated proteasomal degradation. Taken together, our findings provide novel insights into the role of SPSB1 in ovarian cancer cells.

Keywords: Cell survival; Ovarian cancer; SPSB1; Ubiquitination; p21 destabilization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Female
  • Gene Silencing
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Mice
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Stability
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Suppressor of Cytokine Signaling Proteins / physiology*
  • Ubiquitin / metabolism

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • SPSB1 protein, human
  • Suppressor of Cytokine Signaling Proteins
  • Ubiquitin
  • Proteasome Endopeptidase Complex