HTLV-1 tax-associated hTid-1, a human DnaJ protein, is a repressor of IκB kinase β subunit

被引:40
作者
Cheng, H
Cenciarelli, C
Tao, MY
Parks, WP
Cheng-Mayer, C
机构
[1] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA
[2] CNR, Ist Neurobiol & Med Mol, I-00137 Rome, Italy
[3] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA
[4] NYU, Sch Med, Dept Pediat, New York, NY 10016 USA
关键词
D O I
10.1074/jbc.M201204200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
hTid-1, a human DnaJ protein, is a novel cellular target for HTLV-1 Tax. Here, we show that hTid-1 represses NF-kappaB activity induced by Tax as well as other activators such as tumor necrosis factor alpha (TNFalpha) and Bcl10. hTid-1 specifically suppresses serine phosphorylation of IkappaBalpha by activated IkappaB kinase beta (IKKbeta), but the activities of other serine kinases including p38, ERK2, and JNK1 are not affected. The suppressive activity of hTid-1 on IKKbeta requires a functional J domain that mediates association with heat shock proteins and results in prolonging the half-life of the NF-kappaB inhibitors IkappaBalpha and IkappaBbeta. Collectively, our data suggest that hTid-1, in association with heat shock proteins, exerts a negative regulatory effect on the NF-kappaB activity induced by various extracellular and intracellular activators including HTLV-1 Tax.
引用
收藏
页码:20605 / 20610
页数:6
相关论文
共 43 条
[1]
The NF-kappa B and I kappa B proteins: New discoveries and insights [J].
Baldwin, AS .
ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 :649-683
[2]
Transdominant mutants of I kappa B alpha block Tat tumor necrosis factor synergistic activation of human immunodeficiency virus type 1 gene expression and virus multiplication [J].
Beauparlant, P ;
Kwon, H ;
Clarke, M ;
Lin, RT ;
Sonenberg, N ;
Wainberg, M ;
Hiscott, J .
JOURNAL OF VIROLOGY, 1996, 70 (09) :5777-5785
[3]
BOHNLEIN E, 1989, J VIROL, V63, P1578
[4]
Site-specific phosphorylation of I kappa B alpha by a novel ubiquitination-dependent protein kinase activity [J].
Chen, ZJ ;
Parent, L ;
Maniatis, T .
CELL, 1996, 84 (06) :853-862
[5]
Human T cell leukemia virus type 1 Tax associates with a molecular chaperone complex containing hTid-1 and Hsp70 [J].
Cheng, H ;
Cenciarelli, C ;
Shao, ZP ;
Vidal, M ;
Parks, WP ;
Pagano, M ;
Cheng-Mayer, C .
CURRENT BIOLOGY, 2001, 11 (22) :1771-1775
[6]
IKKγ mediates the interaction of cellular IκB kinases with the tax transforming protein of human T cell leukemia virus type 1 [J].
Chu, ZL ;
Shin, YA ;
Yang, JM ;
DiDonato, JA ;
Ballard, DW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (22) :15297-15300
[7]
The tax oncoprotein of human T-cell leukemia virus type 1 associates with and persistently activates IκB kinases containing IKKα and IKKβ [J].
Chu, ZL ;
DiDonato, JK ;
Hawiger, J ;
Ballard, DW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (26) :15891-15894
[8]
Heat shock inhibits radiation-induced activation of NF-κB via inhibition of I-κB kinase [J].
Curry, HA ;
Clemens, RA ;
Shah, S ;
Bradbury, CM ;
Botero, A ;
Goswami, P ;
Gius, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (33) :23061-23067
[9]
Positive and negative regulation of IκB kinase activity through IKKβ subunit phosphorylation [J].
Delhase, M ;
Hayakawa, M ;
Chen, Y ;
Karin, M .
SCIENCE, 1999, 284 (5412) :309-313
[10]
A cytokine-responsive IκB kinase that activates the transcription factor NF-κB [J].
Joseph A. DiDonato ;
Makio Hayakawa ;
David M. Rothwarf ;
Ebrahim Zandi ;
Michael Karin .
Nature, 1997, 388 (6642) :548-554