title: Systematic Analysis of the Functions of Lysine Acetylation in the Regulation of Tat Activity.
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.
authors.affiliation: Center for AIDS Research, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Minghao
authors.initials: M
authors.lastname: He
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhang
authors.forename: Xincheng
authors.initials: X
authors.lastname: Wang
authors.forename: Lihong
authors.initials: L
authors.lastname: Huo
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: Chengye
authors.initials: C
authors.lastname: Feng
authors.forename: Xutian
authors.initials: X
authors.lastname: Jing
authors.forename: Danyao
authors.initials: D
authors.lastname: Du
authors.forename: Huabin
authors.initials: H
authors.lastname: Liang
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Zhangyong
authors.initials: Z
authors.lastname: Hong
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000107:Acetylation; D000409:Alanine / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D001120:Arginine / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D057809:HEK293 Cells; D015497:HIV-1; D006801:Humans; D019169:Jurkat Cells; D008239:Lysine / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D009154:Mutation; D011485:Protein Binding; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D054322:tat Gene Products, Human Immunodeficiency Virus; D005973:Glutamine; D001120:Arginine; D008239:Lysine; D000409:Alanine