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

Ying Liu, Jinliang Li, Byung Oh Kim, Betty Sue Pace, Johnny J. He

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Human immunodeficiency virus type 1 (HIV-1) gene expression and replication is highly dependent on and modulated by interactions between viral and host cellular factors. Tat protein, encoded by one of the HIV-1 regulatory genes, tat, is essential for HIV-1 gene expression. A number of host cellular factors have been shown to interact with Tat in this process. During our attempts to determine the molecular mechanisms of Tat interaction with brain cells, we isolated a cDNA clone that encodes a novel Tat-interacting protein of 110 kDa or Tip110 from a human fetal brain cDNA library. GenBank™ BLAST search revealed that Tip110 was almost identical to a previously cloned KIAA0156 gene with unknown functions. In vivo binding of Tip110 with Tat was confirmed by immunoprecipitation and Western blotting, in combination with mutagenesis. The yeast three-hybrid RNA-protein interaction assay indicated no direct interaction of Tip110 with Tat transactivating response element RNA. Nevertheless, Tip110 strongly synergized with Tat on Tat-mediated chloramphenicol acetyltransferase reporter gene expression and HIV-1 virus production, whereas down-modulation of constitutive Tip110 expression inhibited HIV-1 virus production. Northern blot analysis showed that Tip110 mRNA was expressed in a variety of human tissues and cells. Moreover, digital fluorescence microscopic imaging revealed that Tip110 was expressed exclusively in the nucleus, and within a nuclear speckle structure that has recently been described for human cyclin T and CDK9, two critical components for Tat transactivation function on HIV-1 long terminal repeat promoter. Taken together, these data demonstrate that Tip110 regulates Tat transactivation activity through direct interaction, and suggest that Tip110 is an important cellular factor for HIV-1 gene expression and viral replication.

Original languageEnglish (US)
Pages (from-to)23854-23863
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number26
DOIs
StatePublished - Jun 28 2002
Externally publishedYes

Fingerprint

HIV Long Terminal Repeat
tat Gene Products
Terminal Repeat Sequences
Nuclear Proteins
Viruses
Transcriptional Activation
HIV-1
Gene expression
Proteins
Gene Expression
Cyclin T
RNA
Brain
Chloramphenicol O-Acetyltransferase
Genes
Optical Imaging
Nucleic Acid Databases
Response Elements
Regulator Genes
Gene Library

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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. / Liu, Ying; Li, Jinliang; Kim, Byung Oh; Pace, Betty Sue; He, Johnny J.

In: Journal of Biological Chemistry, Vol. 277, No. 26, 28.06.2002, p. 23854-23863.

Research output: Contribution to journalArticle

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