Journal
CELL CYCLE
Volume 11, Issue 6, Pages 1217-1234Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.11.6.19664
Keywords
Tip60; Plk1; cyclin B1; tat; cell cycle; HIV; phosphorylation
Categories
Funding
- MOST, China [2007CB914603]
- China National Science Foundation [81071361, 30970677]
- Outstanding Youth Scientist Foundation of NFSC, China [30825011]
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HIV-1 Tat triggers intrinsic and extrinsic apoptosis pathways in both infected and uninfected cells and plays an important role in the pathogenesis of AIDS. Knocking down Tip60, an interactive protein of Tat, leads to the impairment of cell cycle progression, indicating a key role of Tip60 in cell cycle control. We found that Tip60 interacts with Plk1 through its ZnF-MYST domain, and that this interaction is enhanced in the G(2)/M phase. In addition, cyclin B1 was confirmed to interact with the ZnF domain of Tip60. Immunofluorescence imaging showed that Tip60 co-localizes with both Plk1 and cyclin B1 at the centrosome during the mitotic phase and to the mid-body during cytokinesis. Further experiments revealed that Tip60 forms a ternary complex with Plk1 and cyclin B1 and acetylates Plk1 but not cyclin B1. HIV-1 Tat likely forms a quaternary complex with Tip60, cyclin B1 and Plk1. Fluorescent microscopy showed that Tat causes an unscheduled nuclear translocation of both cyclin B1 and Plk1, causing their co-localization with Tip60 in the nucleus. Tat, Tip60, cyclin B1 and Plk1 interactions provide new a mechanistic explanation for Tat-mediated cell cycle dysregulation and apoptosis.
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