title: Modulation of the stability and activities of HIV-1 Tat by its ubiquitination and carboxyl-terminal region.
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.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071 China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071 China.
authors.forename: Juan
authors.initials: J
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071 China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071 China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071 China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: He
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071 China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071 China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071 China.
authors.forename: Dengwen
authors.initials: D
authors.lastname: Li
keywords: Activity; Carboxyl-terminal region; Stability; Tat; Ubiquitination