Your browser version may not work well with NCBI's Web applications. More information here...
1: J Virol. 2005 Sep;79(17):11135-41.Click here to read Click here to read Links

Ubiquitylation of Cdk9 by Skp2 facilitates optimal Tat transactivation.

Barboric M, Zhang F, Besenicar M, Plemenitas A, Peterlin BM.

Rosalind Russell Medical Research Center, Department of Medicine, University of California, San Francisco, 94143, USA.

By recruiting the positive transcriptional elongation factor b (P-TEFb) to paused RNA polymerase II, the transactivator Tat stimulates transcriptional elongation of the human immunodeficiency virus type 1 (HIV-1) genome. We found that cyclin-dependent kinase 9 (Cdk9), the catalytic subunit of P-TEFb, is ubiquitylated in vivo. This ubiquitylation depended on the Skp1/Cul1/F-box protein E3 ubiquitin ligase Skp2. Likewise, Tat required Skp2 since its transactivation of the HIV-1 long terminal repeat decreased in primary mouse embryonic fibroblasts, which lacked Skp2. The ubiquitylation of Cdk9 by Skp2 facilitated the formation of the ternary complex between P-TEFb, Tat, and transactivation response element. Thus, our findings underscore the requirement of ubiquitylation for the coactivator function in regulating HIV-1 transcriptional elongation.

PMID: 16103164 [PubMed - indexed for MEDLINE]

PMCID: PMC1193628