HTLV-1 HBZ suppresses AP-1 activity by impairing both the DNA-binding ability and the stability of c-Jun protein.
Disruption of transcriptional control of cellular genes by human T-cell leukemia virus type-1 (HTLV-1) is thought to be associated, at least in part, with the development of adult T-cell leukemia. It has been reported that activating protein-1 (AP-1) is dysregulated by HTLV-1 infection. HTLV-1-encoded Tax elevates AP-1 activity through the induction of AP-1 family member gene expression, including c-Jun, JunD, c-Fos, and Fra-1. However, the precise mechanism by which HTLV-1 regulates AP-1 activity remains to be addressed. Recently, a novel viral protein named HTLV-1 basic leucine-zipper factor, HBZ, has been shown to interact with c-Jun and repress c-Jun-mediated transcription by abrogating its DNA-binding activity. In the course of investigating HBZ function, we found that HBZ reduced the steady-state levels of c-Jun, and the levels were restored by treatment with a proteasome inhibitor. Together, this indicates that HBZ promotes c-Jun degradation through a proteasome-dependent pathway. Furthermore, HBZ deletion mutants revealed that both the N-terminal and leucine-zipper region of HBZ were required for the elimination of c-Jun. These results suggest dual effects of HBZ on the suppression of AP-1 activity by inhibiting c-Jun function, which may contribute to the dysregulation of cell proliferation.
Matsumoto
Jun
J
Laboratory of Human Tumor Viruses, Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Ohshima
Takayuki
T
Isono
Osamu
O
Shimotohno
Kunitada
K
D050976:Basic-Leucine Zipper Transcription Factors; D004247:DNA / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D005786:Gene Expression Regulation; D016758:Genes, jun; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D016350:Leucine Zippers; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000821:virology; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis* / Q000494:pharmacology; D012191:Retroviridae Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors / Q000494:pharmacology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000494:pharmacology*
D050976:Basic-Leucine Zipper Transcription Factors; C479751:HBZ protein, human T-cell leukemia virus type I; D016755:Proto-Oncogene Proteins c-jun; D012191:Retroviridae Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014764:Viral Proteins; D004247:DNA