Human GLI-2 is a tat activation response element-independent Tat cofactor

J Virol. 2001 Mar;75(5):2314-23. doi: 10.1128/JVI.75.5.2314-2323.2001.

Abstract

Zinc finger-containing GLI proteins are involved in the development of Caenorhabditis elegans, Xenopus, Drosophila, zebrafish, mice, and humans. In this study, we show that an isoform of human GLI-2 strongly synergizes with the Tat transactivating proteins of human immunodeficiency virus types 1 and 2 (HIV-1 and -2) and markedly stimulates viral replication. GLI-2 also synergizes with the previously described Tat cofactor cyclin T1 to stimulate Tat function. Surprisingly, GLI-2/Tat synergy is not dependent on either a typical GLI DNA binding site or an intact Tat activation response element but does require an intact TATA box. Thus, GLI-2/Tat synergy results from a mechanism of action which is novel both for a GLI protein and for a Tat cofactor. These findings link the GLI family of transcriptional and developmental regulatory proteins to Tat function and HIV replication.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism*
  • Cell Line
  • Chemoreceptor Cells
  • Cyclin T
  • Cyclins / metabolism
  • Drosophila Proteins
  • Escherichia coli Proteins*
  • Gene Products, tat / genetics*
  • Gene Products, tat / metabolism*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / physiology
  • HIV-2 / genetics
  • HIV-2 / physiology
  • Humans
  • Kruppel-Like Transcription Factors
  • Membrane Proteins / metabolism*
  • Mice
  • Nuclear Proteins
  • Plasmids
  • Receptors, Cell Surface*
  • Response Elements* / genetics
  • TATA Box / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation*
  • Transfection
  • Virus Replication
  • Zinc Finger Protein Gli2
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Bacterial Proteins
  • CCNT1 protein, human
  • Ccnt1 protein, mouse
  • CycT protein, Drosophila
  • Cyclin T
  • Cyclins
  • Drosophila Proteins
  • Escherichia coli Proteins
  • GLI2 protein, human
  • Gene Products, tat
  • Gli2 protein, mouse
  • Kruppel-Like Transcription Factors
  • Membrane Proteins
  • Nuclear Proteins
  • Receptors, Cell Surface
  • Tar protein, E coli
  • Transcription Factors
  • Zinc Finger Protein Gli2
  • tat Gene Products, Human Immunodeficiency Virus