title: HIV-1 Tat impairs cell cycle control by targeting the Tip60, Plk1 and cyclin B1 ternary complex.
abstract: 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 ZnFMYST 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.
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: Maoyong
authors.initials: M
authors.lastname: Song
authors.forename: Tian-Yi
authors.initials: TY
authors.lastname: Yang
authors.forename: Rong
authors.initials: R
authors.lastname: Fan
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Liu
authors.forename: Ping-Kun
authors.initials: PK
authors.lastname: Zhou
mesh_terms: D000107:Acetylation; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D015497:HIV-1 / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D050801:Ternary Complex Factors / Q000235:genetics / Q000378:metabolism; D059008:Time-Lapse Imaging; D014162:Transfection; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D056744:Cyclin B1; D051548:Histone Acetyltransferases; D000074443:Lysine Acetyltransferase 5; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D050801:Ternary Complex Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D000097869:Polo-Like Kinase 1; C534699:CCNB1 protein, human; C098489:KAT5 protein, human