NF-kappa B binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II

To stimulate transcriptional elongation of HIV-1 genes, the transactivator Tat recruits the positive transcription elongation factor b (P-TEFb) to the initiating RNA polymerase II (RNAPII). We found that the activation of tra nscription by ReIA also depends on P-TEFb. Similar to Tat, ReIA activated t ranscription when tethered to RNA. Moreover, TNF-alpha triggered the recrui tment of P-TEFb to the NF-B-K-regulated IL-8 gene. While the formation of t he transcription preinitiation complex (PIC) remained unaffected, DRB, an i nhibitor of P-TEFb, prevented RNAPII from elongating on the IL-8 gene. Rema rkably, DRB inhibition sensitized cells to TNF-alpha -induced apoptosis. Th us, NF-B-K requires P-TEFb to stimulate the elongation of transcription and P-TEFb plays an unexpected role in regulating apoptosis.