Abstract
BACKGROUND: The transactivator of transcription (Tat) protein of human immunodeficiency virus type 1 (HIV-1) is known to undergo ubiquitination. However, the roles of ubiquitination in regulating Tat stability and activities are unclear. In addition, although the 72- and 86-residue forms are commonly used for in vitro studies, the 101-residue form is predominant in the clinical isolates of HIV-1. The influence of the carboxyl-terminal region of Tat on its functions remains unclear. RESULTS: In this study, we find that Tat undergoes lysine 48-linked ubiquitination and is targeted to proteasome-dependent degradation. Expression of various ubiquitin mutants modulates Tat activities, including the transactivation of transcription, induction of apoptosis, interaction with tubulin, and stabilization of microtubules. Moreover, the 72-, 86- and 101-residue forms of Tat also exhibit different stability and aforementioned activities. CONCLUSIONS: Our findings demonstrate that the ubiquitination and carboxyl-terminal region of Tat are critical determinants of its stability and activities.