Depletion of PAK1 enhances Ubiquitin-mediated Survivin degradation in pancreatic β-cells

Yi Chun Chen, Patrick T. Fueger, Zhanxiang Wang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Functional β-cell mass deficiency in diabetes results from imbalanced β-cell death and replication, and decreased PAK1 protein levels in human islets from donors with type 2 diabetes implicates a possible role for PAK1 in maintaining β-cell mass. Here, we aim to address the linkage between PAK1 and Survivin, a protein essential for β-cell replication. PAK1 knockout (KO) mouse islets exhibited decreased expression of Survivin protein. MIN6 β-cells with siRNA-mediated suppression of PAK1 also had decreased Survivin protein and exhibited an increased level of ubiquitinated-Survivin. However, no significant changes in Survivin mRNA were found in islets from PAK1 KO mice and PAK1-depleted MIN6 β-cells. The decreased Survivin level in MIN6 cells subjected to hyperglycemic stress was prevented by expression of exogenous PAK1. Moreover, overexpressing Survivin restored proliferation of β-cells that was impaired by the loss of PAK1. These data implicate a role for PAK1 in regulating Survivin protein stability in the β-cell and suggest PAK1 as a potential molecular target for the restoration of β-cell mass.

Original languageEnglish
Pages (from-to)22-28
Number of pages7
JournalIslets
Volume5
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Ubiquitin
Knockout Mice
Proteins
Protein Stability
Type 2 Diabetes Mellitus
Small Interfering RNA
Cell Death
Cell Proliferation
Messenger RNA

Keywords

  • MIN6
  • Mouse islet
  • PAK1
  • Pancreatic β-cell
  • Replication
  • Survivin
  • Ubiquitination

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Depletion of PAK1 enhances Ubiquitin-mediated Survivin degradation in pancreatic β-cells. / Chen, Yi Chun; Fueger, Patrick T.; Wang, Zhanxiang.

In: Islets, Vol. 5, No. 1, 01.2013, p. 22-28.

Research output: Contribution to journalArticle

Chen, Yi Chun ; Fueger, Patrick T. ; Wang, Zhanxiang. / Depletion of PAK1 enhances Ubiquitin-mediated Survivin degradation in pancreatic β-cells. In: Islets. 2013 ; Vol. 5, No. 1. pp. 22-28.
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