Yr. Zhu et al., TRANSCRIPTION ELONGATION-FACTOR P-TEFB IS REQUIRED FOR HIV-1 TAT TRANSACTIVATION IN-VITRO, Genes & development, 11(20), 1997, pp. 2622-2632
P-TEFb is a key regulator of the process controlling the processivity-
of RNA polymerase II and possesses a kinase activity that can phosphor
ylate the carboxy-terminal domain of the largest subunit of RNA polyme
rase II. Here we report the cloning of the small subunit of Drosophila
P-TEFb and the finding that it encodes a Cdc2-related protein kinase.
Sequence comparison suggests that a protein with 72% identity, PITALR
E, could be the human homolog of the Drosophila protein. Functional ho
mology was suggested by transcriptional analysis of an RNA polymerase
II promoter with HeLa nuclear extract depleted of PITALRE. Because the
depleted extract lost the ability to produce long DRB-sensitive trans
cripts and this loss was reversed by the addition of purified Drosophi
la P-TEFb, we propose that PITALRE is a component of human P-TEFb. In
addition, we found that PITALRE associated with the activation domain
of HIV-1 Tat, indicating that P-TEFb is a Tat-associated kinase (TAK).
An in vitro transcription assay demonstrates that the effect of Tat o
n transcription elongation requires P-TEFb and suggests that the enhan
cement of transcriptional processivity by Tat is attributable to enhan
ced function of P-TEFb on the HIV-1 LTR.