p14^ARF is capable of promoting HIV-1 Tat degradation

Abstract

The p14^ARF tumor suppressor functions as ʻoncogenic 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 p14ARF 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 ubiquitinindependent pathway.