Tip110 protein binds to unphosphorylated RNA polymerase II and promotes its phosphorylation and HIV-1 long terminal repeat transcription.
Transcription plays an important role in both HIV-1 gene expression and replication and mandates complicated but coordinated interactions between the host and virus. Our previous studies have shown that an HIV-1 Tat-interacting protein of 110 kDa, Tip110, binds to and enhances Tat function in Tat-mediated HIV-1 gene transcription and replication (Liu, Y., Li, J., Kim, B. O., Pace, B. S., and He, J. J. (2002) HIV-1 Tat protein-mediated transactivation of the HIV-1 long terminal repeat promoter is potentiated by a novel nuclear Tat-interacting protein of 110 kDa, Tip110. J. Biol. Chem. 277, 23854-23863). However, the underlying molecular mechanisms by which this takes place were not understood. In this study, we demonstrated that Tip110 bound to unphosphorylated RNA polymerase II (RNAPII) in a direct and specific manner. In addition, we detected Tip110 at the HIV-1 long terminal repeat (LTR) promoter and found that Tip110 expression was associated with increased phosphorylation of serine 2 of the heptapeptide repeats within the RNAPII C-terminal domain and increased recruitment of positive transcription elongation factor b to the LTR promoter. Consistent with these findings, we showed that Tip110 interaction with Tat directly enhanced transcription elongation of the LTR promoter. Taken together, these findings have provided additional and mechanistic evidence to support Tip110 function in HIV-1 transcription.
From the Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202 and.
Weina
W
Zhao
Ying
Y
Liu
Khalid Amine
KA
Timani
Johnny J
JJ
He
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D061805:Transcription Elongation, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
D000951:Antigens, Neoplasm; D016601:RNA-Binding Proteins; C416530:SART3 protein, human; D054322:tat Gene Products, Human Immunodeficiency Virus; D012319:RNA Polymerase II
HIV-1; Long Terminal Repeat; Phosphorylation; Promoters; RNA Polymerase II; Tip110; Transcription; Transcription Elongation; Transcription Initiation; Viral Replication