Abstract
The Tat protein of HIV-1 has several well-known properties, such as nucleocytoplasmic trafficking, transactivation of transcription, interaction with tubulin, regulation of mitotic progression, and induction of apoptosis. Previous studies have identified a couple of lysine residues in Tat that are essential for its functions. In order to analyze the functions of all the lysine residues in Tat, we mutated them individually to alanine, glutamine, and arginine. Through systematic analysis of the lysine mutants, we discovered several previously unidentified characteristics of Tat. We found that lysine acetylation could modulate the subcellular localization of Tat, in addition to the regulation of its transactivation activity. Our data also revealed that lysine mutations had distinct effects on microtubule assembly and Tat binding to bromodomain proteins. By correlation analysis, we further found that the effects of Tat on apoptosis and mitotic progression were not entirely attributed to its effect on microtubule assembly. Our findings suggest that Tat may regulate diverse cellular activities through binding to different proteins and that the acetylation of distinct lysine residues in Tat may modulate its interaction with various partners.
Highlights
The Tat protein plays an essential role in the life cycle of HIV-1
Lysine acetylation, which leads to the formation of a neutral and hydrophobic side chain, is able to modulate diverse proteinprotein interactions [27,28]
Through systematic analysis of the effects of the lysine mutations on Tat subcellular localization and its activities towards HIV-1 transcription, microtubule assembly, mitotic progression, apoptosis, and binding to bromodomain proteins, we have identified several interesting features of Tat
Summary
The Tat protein plays an essential role in the life cycle of HIV-1. Tat has many biological functions, such as transactivation of transcription, regulation of mitotic progression, and induction of apoptosis [1,2,3,4]. Like the activators of many other viruses, Tat regulates HIV-1 gene transcription primarily through association with host cellular factors. This process provides a positive feedback cycle, allowing HIV-1 to have an explosive response to defeat the body’s response. Tat can act directly as a toxin to induce apoptosis in uninfected ‘‘bystander’’ cells [1,2,3,5]. The mechanism of action of this small protein remains incompletely understood
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