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© Research
Publication : Oncogene

AP-1 dimers regulate transcription of the p14/p19ARF tumor suppressor gene

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Oncogene - 31 Mar 2005

Ameyar-Zazoua M, Wisniewska MB, Bakiri L, Wagner EF, Yaniv M, Weitzman JB

Link to Pubmed [PMID] – 15688012

Oncogene 2005 Mar;24(14):2298-306

Evidence is accumulating about the role of individual AP-1 components in cell proliferation and transformation. Notably, Ras-mediated transformation is characterized by the upregulation of particular AP-1 members, such as c-Jun and Fra-1. The p14/p19ARF tumor suppressor gene is a key link between oncogenic Ras signaling and the p53 pathway. We explored the involvement of AP-1 dimers in the transcriptional regulation of the p14/p19ARF gene. We demonstrate that both the human and mouse ARF promoters are transcriptional targets of selective AP-1 dimers. The ARF promoter is regulated specifically by AP-1 heterodimers containing Fra-1. Overexpression of c-Jun approximately Fra-1 dimers in primary murine fibroblast cells led to the upregulation of the endogenous ARF protein and growth arrest. Conversely, inhibition of c-Jun or Fra-1 protein levels resulted in decreased ARF expression. In addition, we show that AP-1 dimers cooperate with oncogenic Ras in the transcriptional activation of the p14/p19ARF promoter. Thus, AP-1 heterodimers may contribute to the regulation of ARF expression upon oncogenic signaling.

http://www.ncbi.nlm.nih.gov/pubmed/15688012