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

M Barboric; R M Nissen; S Kanazawa; N Jabrane-Ferrat; B M Peterlin

doi:10.1016/s1097-2765(01)00314-8

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

Mol Cell. 2001 Aug;8(2):327-37. doi: 10.1016/s1097-2765(01)00314-8.

Authors

M Barboric¹, R M Nissen, S Kanazawa, N Jabrane-Ferrat, B M Peterlin

Affiliation

¹ Howard Hughes Medical Institute Departments of Medicine, Microbiology, and Immunology University of California at San Francisco 94143, USA.

PMID: 11545735
DOI: 10.1016/s1097-2765(01)00314-8

Abstract

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 transcription by RelA also depends on P-TEFb. Similar to Tat, RelA activated transcription when tethered to RNA. Moreover, TNF-alpha triggered the recruitment of P-TEFb to the NF-kappaB-regulated IL-8 gene. While the formation of the transcription preinitiation complex (PIC) remained unaffected, DRB, an inhibitor of P-TEFb, prevented RNAPII from elongating on the IL-8 gene. Remarkably, DRB inhibition sensitized cells to TNF-alpha-induced apoptosis. Thus, NF-kappaB requires P-TEFb to stimulate the elongation of transcription and P-TEFb plays an unexpected role in regulating apoptosis.

Publication types

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

MeSH terms

Apoptosis / physiology
DNA-Binding Proteins / metabolism
Dichlororibofuranosylbenzimidazole / pharmacology
Gene Products, tat / metabolism
Genes, Reporter
HIV-1 / genetics
HIV-1 / metabolism
Humans
Interleukin-8 / genetics
NF-kappa B / genetics
NF-kappa B / metabolism*
Nucleic Acid Synthesis Inhibitors / pharmacology
Positive Transcriptional Elongation Factor B
Protein Serine-Threonine Kinases / metabolism*
RNA Polymerase II / metabolism*
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Transcription Factor RelA
Transcription, Genetic / physiology*
Transcriptional Activation
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha / metabolism
tat Gene Products, Human Immunodeficiency Virus

Substances

DNA-Binding Proteins
Gene Products, tat
Interleukin-8
NF-kappa B
Nucleic Acid Synthesis Inhibitors
Recombinant Fusion Proteins
Transcription Factor RelA
Tumor Necrosis Factor-alpha
tat Gene Products, Human Immunodeficiency Virus
Dichlororibofuranosylbenzimidazole
Positive Transcriptional Elongation Factor B
Protein Serine-Threonine Kinases
RNA Polymerase II