AMF-1/Gps2 binds p300 and enhances its interaction with papillomavirus E2 proteins

J Virol. 2000 Jul;74(13):5872-9. doi: 10.1128/jvi.74.13.5872-5879.2000.

Abstract

The cellular protein AMF-1 (Gps2) positively modulates gene expression by the papillomavirus E2 protein (D. E. Breiding et al., Mol. Cell. Biol. 17:7208-7219, 1997). We show here that AMF-1 also binds the transcriptional coactivator p300 in vitro and in vivo. E2 interacted weakly with p300. These observations led to a model in which AMF-1 recruits p300 into a complex with E2. Cotransfection of AMF-1 or p300 stimulated levels of E2-dependent transcription, while cotransfection of both AMF-1 and p300 showed an additive effect. The functional significance of p300 recruitment for E2 transactivation was evidenced by repression of E2-activated transcription by adenovirus E1A, which inhibits both coactivator and acetylase activities of p300. Antibodies to AMF-1 or E2 immunoprecipitated histone acetylase activity from cell lysates. Western blotting using antibody against acetyl-lysine failed to detect acetylation of AMF-1 or E2 in complex with p300. These results suggest that AMF-1 facilitates the recruitment of p300 and its histone acetylase activity into complexes with E2 and represents a novel mechanism of transcriptional activation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylation
  • Adenovirus E1A Proteins / genetics
  • Adenovirus E1A Proteins / metabolism
  • Animals
  • Binding Sites
  • Bovine papillomavirus 1*
  • Cattle
  • Cell Line
  • Chemical Precipitation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Histones / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins*
  • Spodoptera / cytology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*

Substances

  • Adenovirus E1A Proteins
  • DNA-Binding Proteins
  • E1 protein, Bovine papillomavirus
  • E2 protein, Bovine papillomavirus
  • E2 protein, Human papillomavirus type 16
  • Fungal Proteins
  • GPS2 protein, human
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Oncogene Proteins, Viral
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Trans-Activators
  • Viral Proteins