The HTLV-1 HBZ protein inhibits cyclin D1 expression through interacting with the cellular transcription factor CREB.
Human T cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that can cause adult T-cell leukemia (ATL) and other diseases. The HTLV-1 bZIP factor (HBZ), which is encoded by an mRNA of the opposite polarity of the viral genomic RNA, interacts with several transcription factors and is involved in T cell proliferation, viral gene transcription and cellular transformation. Cyclin D1 is a pivotal regulatory protein involved in cell cycle progression, and its depressed expression correlates with cell cycle prolongation or arrested at the G1/S transition. In our present study, we observed that HBZ expression suppressed cyclin D1 level. To investigate the role of HBZ on cyclin D1 depression, we transduced HBZ with lentivirus vector into 293T cells, CEM cells and Jurkat cells. The results of Western blot, RT-PCR and luciferase assays showed that transcriptional activity of the cyclin D1 promoter was suppressed by the bZIP domain of HBZ (HBZ-bZIP) through cyclic AMP response element (CRE) site. Immunoprecipitation and GST pull-down assays showed the binding of HBZ-bZIP to CRE-binding protein (CREB), which confirmed that the cyclin D1 promoter activity inhibition via the CRE-site was mediated by HBZ-bZIP. The results suggested that HBZ suppressed cyclin D1 transcription through interactions with CREB and along with other viral protein, HBZ may play a causal role for leukemogenesis.
College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
Yunyun
Y
Ma
Shangen
S
Zheng
Yuanyuan
Y
Wang
Wenqiao
W
Zang
Min
M
Li
Na
N
Wang
Ping
P
Li
Jing
J
Jin
Ziming
Z
Dong
Guoqiang
G
Zhao
D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012191:Retroviridae Proteins; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
D050976:Basic-Leucine Zipper Transcription Factors; D017362:Cyclic AMP Response Element-Binding Protein; C479751:HBZ protein, human T-cell leukemia virus type I; D012191:Retroviridae Proteins; D014764:Viral Proteins; D019938:Cyclin D1