Human GLI-2 is a tat activation response element-independent Tat cofactor.
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.
Browning
C M
CM
Department of Microbiology and Immunology, Ann Arbor, Michigan 48109-0640,USA.
Smith
M J
MJ
Clark
N M
NM
Lane
B R
BR
Parada
C
C
Montano
M
M
KewalRamani
V N
VN
Littman
D R
DR
Essex
M
M
Roeder
R G
RG
Markovitz
D M
DM
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D002628:Chemoreceptor Cells; D056906:Cyclin T; D016213:Cyclins / Q000378:metabolism; D029721:Drosophila Proteins; D029968:Escherichia coli Proteins; D015696:Gene Products, tat / Q000235:genetics* / Q000378:metabolism*; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology; D015498:HIV-2 / Q000235:genetics / Q000502:physiology; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins; D010957:Plasmids; D011956:Receptors, Cell Surface; D020218:Response Elements / Q000235:genetics; D016385:TATA Box / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014779:Virus Replication; D000075746:Zinc Finger Protein Gli2; D054322:tat Gene Products, Human Immunodeficiency Virus
D001426:Bacterial Proteins; C503684:CCNT1 protein, human; C503685:Ccnt1 protein, mouse; C503687:CycT protein, Drosophila; D056906:Cyclin T; D016213:Cyclins; D029721:Drosophila Proteins; D029968:Escherichia coli Proteins; C082593:GLI2 protein, human; D015696:Gene Products, tat; C000618551:Gli2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; C057331:Tar protein, E coli; D014157:Transcription Factors; D000075746:Zinc Finger Protein Gli2; D054322:tat Gene Products, Human Immunodeficiency Virus