p14ARF is capable of promoting HIV-1 tat degradation

Abstract

The p14ARF tumor suppressor functions as 'oncogenic checkpoint' that prevents unrestricted cellular proliferation in response to oncogenic signaling. Albeit, the major pathway through which ARF operates is the ARF-Mdm2-p53 axis, ARF directly binds to and inactivates transcription function of a number of DNA-bound activators. In the present study we show that p14 ARF inhibits transcription activation of HIV-1 LTR promoter activity by Tat protein. Tat protein is a RNA-bound transcriptional activator whose function is strictly required for HIV-1 replication. We determined that p14 ARF inhibits Tat transactivation of HIV-1 LTR by promoting Tat degradation via an ubiquitin-independent pathway. ©2008 Landes Bioscience.