HIV-1 Tat regulates cyclin B1 by promoting both expression and degradation.
Cyclin B1, an important cell cycle regulator, was up-regulated in lymphocytes of human immunodeficiency virus (HIV)-infected patients. However, the mechanism of cyclin B1 up-regulation and the effects of the up-regulation on the host cells remain unclear. Here, we show that HIV-encoded Tat protein regulates cyclin B1 levels in two different ways: first, Tat stimulates the transcription of cyclin B1, which increases cyclin B1 levels and promotes the cells apoptosis; and second, Tat stimulates polyubiquitination-mediated degradation of cyclin B1 through binding to the N-terminal of cyclin B1 (aa 61-129) that is just downstream of the D box, which prevents excessive levels of cyclin B1 in the cells. These results suggest that Tat-regulating cyclin B1 affects the status of HIV: Tat stimulates cyclin B1 expression to slow down the host cell cycle progress and to promote the host cell apoptosis, which might facilitate HIV release; Tat stimulates cyclin B1 degradation to prevent overaccumulation of cyclin B1, which might facilitate HIV replication. Taken together, our results reveal for the first time how HIV-Tat regulates cyclin B1 and keeps its balance in the cells.
Zhang
Shi-Meng
SM
Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing, China.
Sun
Yi
Y
Fan
Rong
R
Xu
Qin-Zhi
QZ
Liu
Xiao-Dan
XD
Zhang
Xiangming
X
Wang
Ya
Y
Zhou
Ping-Kun
PK
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D056744:Cyclin B1 / Q000096:biosynthesis / Q000378:metabolism*; D015870:Gene Expression; D015658:HIV Infections / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000502:physiology*
D056744:Cyclin B1; D054322:tat Gene Products, Human Immunodeficiency Virus