Premium
Tat acetylation regulates its actions on microtubule dynamics and apoptosis in T lymphocytes
Author(s) -
Huo Lihong,
Li Dengwen,
Sun Lei,
Liu Min,
Shi Xingjuan,
Sun Xiaoou,
Li Jingyu,
Dong Bin,
Dong Xin,
Zhou Jun
Publication year - 2011
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2768
Subject(s) - acetylation , microtubule , apoptosis , dynamics (music) , microbiology and biotechnology , chemistry , biology , physics , biochemistry , gene , acoustics
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. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.