Tat acetylation regulates its actions on microtubule dynamics and apoptosis in T lymphocytes.
The transactivator protein Tat of human immunodeficiency virus type 1 (HIV-1) is known to suppress microtubule dynamics and thereby trigger apoptosis in T lymphocytes. These actions of Tat constitute one of the major mechanisms for the massive destruction of T lymphocytes associated with the acquired immunodeficiency syndrome. Herein, we show that Tat acetylation at lysine-28 (K28) enhances its interaction with microtubules and increases its activity to promote microtubule assembly, by lowering the critical concentration of tubulin for polymerization into microtubules. In addition, K28 acetylation enhances the ability of Tat to stabilize microtubules, leading to increased apoptosis in T lymphocytes. Our data further reveal that Tat acetylation at K28 stimulates its activity to induce the translocation of Bim, a pro-apoptotic protein of the Bcl-2 family, from microtubules to mitochondria. These findings provide the first evidence that Tat acetylation regulates its actions on microtubule dynamics and apoptosis, in addition to the regulation of its transactivation activity.
Huo
Lihong
L
Department of Genetics and Cell Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China.
Li
Dengwen
D
Sun
Lei
L
Liu
Min
M
Shi
Xingjuan
X
Sun
Xiaoou
X
Li
Jingyu
J
Dong
Bin
B
Dong
Xin
X
Zhou
Jun
J
D000107:Acetylation; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008239:Lysine / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism* / Q000648:ultrastructure; D014162:Transfection; D014178:Translocation, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism* / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D008239:Lysine