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Enhancement of nuclear factor-kappa B acetylation by coactivator p300 and HIV-1 Tat proteins.

Nuclear factor (NF)-kappaB transcription factors are involved in the control of a large number of normal cellular and organismal processes, such as immune and inflammatory responses, developmental processes, cellular growth, and apoptosis. Transcription of the human immunodeficiency virus type 1 (HIV-1) genome depends on the intracellular environment where the integrate viral DNA is regulated by a complex interplay among viral regulatory proteins, such as Tat, and host cellular transcription factors, such as NF-kappaB, interacting with the viral long terminal repeat region. CBP (CREB-binding protein) and p300, containing an intrinsic histone acetyltransferase (HAT) activity, have emerged as coactivators for various DNA-binding transcription factors. Here, we show that the p50 subunit as well as the p50/p65 of NF-kappaB, and not other factors such as SP1, TFIIB, polymerase II, TFIIA, or p65, can be acetylated by CBP/p300 HAT domain. Acetylation of p50 was completely dependent on the presence of both HAT domain and Tat proteins, implying that Tat influences the transcription machinery by aiding CBP/p300 to acquire new partners and increase its functional repertoire. Three lysines, Lys-431, Lys-440, and Lys-441 in p50 were all acetylated in vitro, and a sequence similarity among p50, p53, Tat, and activin receptor type I on these particular lysines was observed. All proteins have been shown to be acetylated by the CBP/p300 HAT domain. Acetylated p50 increases its DNA binding properties, as evident by streptavidin/biotin pull-down assays when using labeled NF-kappaB oligonucleotides. Increased DNA binding on HIV-1 long terminal repeat coincided with increases in the rate of transcription. Therefore, we propose that acetylation of the DNA binding domain of NF-kappaB aids in nuclear translocation and enhanced transcription and also suggest that the substrate specificity of CBP/p300 can be altered by small peptide molecules, such as HIV-encoded Tat.

Pubmed ID: 11739381

Authors

  • Furia B
  • Deng L
  • Wu K
  • Baylor S
  • Kehn K
  • Li H
  • Donnelly R
  • Coleman T
  • Kashanchi F

Journal

The Journal of biological chemistry

Publication Data

February 15, 2002

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI13969
  • Agency: NIAID NIH HHS, Id: AI43894
  • Agency: NIAID NIH HHS, Id: AI44357

Mesh Terms

  • Acetylation
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cells, Cultured
  • DNA
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Gene Products, tat
  • Glutathione Transferase
  • HIV-1
  • Humans
  • Insects
  • Lysine
  • Mass Spectrometry
  • Molecular Sequence Data
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • Nuclear Proteins
  • Plasmids
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins
  • Sequence Homology, Amino Acid
  • Trans-Activators
  • Transcription Factor RelA
  • Transcription, Genetic
  • tat Gene Products, Human Immunodeficiency Virus