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.

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