STRAP regulates c-Jun ubiquitin-mediated proteolysis and cellular proliferation

Jennifer Reiner, Fei Ye, Nilesh Kashikar, Pran K. Datta

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

STRAP is a ubiquitous WD40 protein that has been implicated in tumorigenesis. Previous studies suggest that STRAP imparts oncogenic characteristics to cells by promoting ERK and pRb phosphorylation. While these findings suggest that STRAP can activate mitogenic signaling pathways, the effects of STRAP on other MAPK pathways have not been investigated. Herein, we report that STRAP regulates the expression of the c-Jun proto-oncogene in mouse embryonic fibroblasts. Loss of STRAP expression results in reduced phospho-c-Jun and total c-Jun but does not significantly reduce the level of two other early response genes, c-Myc and c-Fos. STRAP knockout also decreases expression of the AP-1 target gene, cyclin D1, which is accompanied by a reduction in cell growth. No significant differences in JNK activity or basal c-Jun mRNA levels were observed between wild type and STRAP null fibroblasts. However, proteasomal inhibition markedly increases c-Jun expression in STRAP knockout MEFs and STRAP over-expression decreases the ubiquitylation of c-Jun in 293T cells. Loss of STRAP accelerates c-Jun turnover in fibroblasts and ectopic over-expression of STRAP in STRAP null fibroblasts increases c-Jun expression. Collectively, our findings indicate that STRAP regulates c-Jun stability by decreasing the ubiquitylation and proteosomal degradation of c-Jun.

Original languageEnglish (US)
Pages (from-to)372-377
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume407
Issue number2
DOIs
StatePublished - Apr 8 2011
Externally publishedYes

Fingerprint

Proteolysis
Fibroblasts
Ubiquitin
Cell Proliferation
Ubiquitination
Genes
bcl-1 Genes
jun Genes
Phosphorylation
myc Genes
HEK293 Cells
Cyclin D1
Transcription Factor AP-1
Cell growth
Carcinogenesis
Degradation
Messenger RNA
Growth
Proteins

Keywords

  • C-Jun
  • Cancer
  • STRAP
  • Ubiquitylation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

STRAP regulates c-Jun ubiquitin-mediated proteolysis and cellular proliferation. / Reiner, Jennifer; Ye, Fei; Kashikar, Nilesh; Datta, Pran K.

In: Biochemical and Biophysical Research Communications, Vol. 407, No. 2, 08.04.2011, p. 372-377.

Research output: Contribution to journalArticle

Reiner, Jennifer ; Ye, Fei ; Kashikar, Nilesh ; Datta, Pran K. / STRAP regulates c-Jun ubiquitin-mediated proteolysis and cellular proliferation. In: Biochemical and Biophysical Research Communications. 2011 ; Vol. 407, No. 2. pp. 372-377.
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