HIV-1 Tat 的泛素化和羧基末端区域对其稳定性和活性的调节。

Modulation of the stability and activities of HIV-1 Tat by its ubiquitination and carboxyl-terminal region.

机构信息

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071 China.

出版信息

Cell Biosci. 2014 Oct 7;4(1):61. doi: 10.1186/2045-3701-4-61. eCollection 2014.

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.

背景

人类免疫缺陷病毒 1 型（HIV-1）的转录激活蛋白（Tat）已知会发生泛素化。然而，泛素化在调节 Tat 稳定性和活性方面的作用尚不清楚。此外，尽管 72 个和 86 个残基的形式常用于体外研究，但在 HIV-1 的临床分离物中，101 个残基的形式占优势。Tat 的羧基末端区域对其功能的影响仍不清楚。

结果

在这项研究中，我们发现 Tat 经历赖氨酸 48 位连接的泛素化，并被靶向到蛋白酶体依赖性降解。各种泛素突变体的表达调节 Tat 的活性，包括转录的反式激活、细胞凋亡的诱导、与微管蛋白的相互作用以及微管的稳定。此外，Tat 的 72 个、86 个和 101 个残基形式也表现出不同的稳定性和上述活性。