title: Regulation of Tat acetylation and transactivation activity by the microtubule-associated deacetylase HDAC6.
abstract: Reversible acetylation of Tat is critical for its transactivation activity toward HIV-1 transcription. However, the enzymes involved in the acetylation/deacetylation cycles have not been fully characterized. In this study, by yeast two-hybrid assay, we have discovered the histone deacetylase HDAC6 to be a binding partner of Tat. Our data show that HDAC6 interacts with Tat in the cytoplasm in a microtubule-dependent manner. In addition, HDAC6 deacetylates Tat at Lys-28 and thereby suppresses Tat-mediated transactivation of the HIV-1 promoter. Inactivation of HDAC6 promotes the interaction of Tat with cyclin T1 and leads to an increase in Tat transactivation activity. These findings establish HDAC6 as a Tat deacetylase and support a model in which Lys-28 deacetylation decreases Tat transactivation activity through affecting the ability of Tat to form a ribonucleoprotein complex with cyclin T1 and the transactivation-responsive RNA.
authors.affiliation: Department of Genetics and Cell Biology, Key Laboratory of Molecular Microbiology and Biotechnology of the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Huo
authors.forename: Dengwen
authors.initials: D
authors.lastname: Li
authors.forename: Xiaoou
authors.initials: X
authors.lastname: Sun
authors.forename: Xingjuan
authors.initials: X
authors.lastname: Shi
authors.forename: Prasanthi
authors.initials: P
authors.lastname: Karna
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Wentao
authors.initials: W
authors.lastname: Qiao
authors.forename: Ritu
authors.initials: R
authors.lastname: Aneja
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000107:Acetylation; D000818:Animals; D056906:Cyclin T / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: C503684:CCNT1 protein, human; C503685:Ccnt1 protein, mouse; D056906:Cyclin T; D054322:tat Gene Products, Human Immunodeficiency Virus; C433811:HDAC6 protein, human; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases