title: HIV-1 Tat regulates cyclin B1 by promoting both expression and degradation.
abstract: 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.
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Shi-Meng
authors.initials: SM
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.forename: Rong
authors.initials: R
authors.lastname: Fan
authors.forename: Qin-Zhi
authors.initials: QZ
authors.lastname: Xu
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Liu
authors.forename: Xiangming
authors.initials: X
authors.lastname: Zhang
authors.forename: Ya
authors.initials: Y
authors.lastname: Wang
authors.forename: Ping-Kun
authors.initials: PK
authors.lastname: Zhou
mesh_terms: 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*
chemical_list: D056744:Cyclin B1; D054322:tat Gene Products, Human Immunodeficiency Virus