Activation of c-Jun N-terminal kinase (JNK) pathway by HSV-1 immediate early protein ICP0.
The immediate early protein ICP0 encoded by herpes simplex virus 1 (HSV-1) is believed to activate transcription and consequently productive infection. The precise mechanisms of ICP0-mediated transactivation are under intensive study. Here, we demonstrate that ICP0 can strongly activate AP-1 responsive genes specifically. This activation is inhibited by c-Jun (S73A), c-Jun (S63/73A), TAK1 (K63W), but not by p38 (AF), ERK1 (K71R), ERK2 (K52R) and TRAF6 (C85A/H87A). We further investigate the relevancy of ERK, JNK and p38 MAPK pathways using their respective inhibitors PD98059, SP600125 and SB202190. Only SP600125 significantly attenuates the AP-1 responsive gene activation by ICP0. Consistent with these, the JNK is remarkably activated in response to ICP0, and this JNK activation is shown to be significantly attenuated by TAK1 (K63W). It turns out that ICP0 interacts specifically with TAK1 and stimulates its kinase activity. These findings reveal a new molecular mechanism ICP0 explores to regulate gene expression.
Diao
Lirong
L
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, PR China.
Zhang
Bianhong
B
Xuan
Chenghao
C
Sun
Shaogang
S
Yang
Kai
K
Tang
Yujie
Y
Qiao
Wentao
W
Chen
Qimin
Q
Geng
Yunqi
Y
Wang
Chen
C
D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation / Q000502:physiology; D000099151:MAP Kinase Kinase Kinase 7
D017874:Immediate-Early Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D018808:Transcription Factor AP-1; D044767:Ubiquitin-Protein Ligases; D000099151:MAP Kinase Kinase Kinase 7; C051804:Vmw110 protein, Human herpesvirus 1