Propensity for HBZ-SP1 isoform of HTLV-I to inhibit c-Jun activity correlates with sequestration of c-Jun into nuclear bodies rather than inhibition of its DNA-binding activity
Propensity for HBZ-SP1 isoform of HTLV-I to inhibit c-Jun activity correlates with sequestration of c-Jun into nuclear bodies rather than inhibition of its DNA-binding activity
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DOI：
10.1016/j.virol.2009.06.027
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发表时间：
2009-09-01
期刊：
影响因子：
3.7
通讯作者：
Mesnard, Jean-Michel
中科院分区：
文献类型：
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作者：
Clerc, Isabelle;Hivin, Patrick;Mesnard, Jean-Michel
HTLV-I bZIP因子(HBZ)含有一个C-末端的拉链结构域，参与了与c-Jun.这种相互作用导致c-jun DNA结合活性降低，并阻止该蛋白激活AP-1依赖的启动子的转录。然而，目前尚不清楚HBZ-SP1的负面作用是由于其弱的DNA结合活性，还是由于其靶向转录不活跃的核体的细胞因子的能力。为了回答这个问题，我们制作了一个突变体，将HBZ-SP1的调节域和DNA结合域中的特定残基替换为相应的c-Fos氨基酸，以提高c-Jun/HBZ-SP1异源二聚体的DNA结合活性。对突变体的稳定性、与c-jun的相互作用、杂二聚体的DNA结合活性以及对c-jun活性的影响进行了检测。综上所述，我们证明体内c-jun活性的抑制主要是由于HBZ-SP1介导的c-jun对HBZ-NBS的截留。(C)2009 Elsevier Inc.保留所有权利。
HTLV-I bZIP factor (HBZ) contains a C-terminal zipper domain involved in its interaction with c-Jun. This interaction leads to a reduction of c-Jun DNA-binding activity and prevents the protein from activating transcription of AP-1-dependent promoters. However, it remained unclear whether the negative effect of HBZ-SP1 was due to its weak DNA-binding activity or to its capacity to target Cellular factors to transcriptionally-inactive nuclear bodies. To answer this question, we produced a Mutant in which specific residues present in the modulatory and DNA-binding domain of HBZ-SP1 were substituted for the corresponding c-Fos amino acids to improve the DNA-binding activity of the c-Jun/HBZ-SP1 heterodimer. The stability of the mutant, its interaction with c-Jun, DNA-binding activity of the resulting heterodimer, and its effect on the c-Jun activity were tested. In conclusion, we demonstrate that the repression of c-Jun activity in vivo is mainly due to the HBZ-SP1-mediated sequestration of c-Jun to the HBZ-NBs. (C) 2009 Elsevier Inc. All rights reserved.