Rb enhances p160/SRC coactivator-dependent activity of nuclear receptors and hormone responsiveness

J Biol Chem. 2005 May 20;280(20):19746-56. doi: 10.1074/jbc.M413428200. Epub 2005 Mar 14.

Abstract

The retinoblastoma tumor suppressor protein (Rb) is best known as a repressor of genes involved in cell cycle progression. Rb has also been implicated in activation of transcription, in particular by nuclear receptors (NRs) and by differentiation-related transcription factors, but the relevance of this activity is unclear. We show that Rb and the related proteins p107 and p130 enhance the activity of NRs related to NGFI-B (Nur factors) through direct interactions with NGFI-B and SRC-2. Although recruitment of SRC/p160 coactivators to the NGFI-B AF1 domain is independent of Rb, its presence enhances SRC-dependent transcription. Rb potentiation of SRC coactivators is exerted on a subset (Nur factors, hepatocyte nuclear factor-4 (HNF-4), SF-1, and ER) but not all NRs. The levels of Rb-related proteins modulate hormone responsiveness of the NGFI-B-dependent pituitary proopiomelanocortin gene and HNF-4-dependent transcription during enterocyte differentiation. Increased Rb expression upon cell differentiation may promote differentiated functions, at least in part, by potentiation of NR activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Caco-2 Cells
  • Cell Line
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Humans
  • Kinetics
  • L Cells
  • Mice
  • Models, Biological
  • Multiprotein Complexes
  • Nuclear Receptor Coactivator 2
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Pro-Opiomelanocortin / genetics
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • RNA, Small Interfering / genetics
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Steroid / chemistry
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Retinoblastoma Protein / chemistry
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transfection

Substances

  • DNA-Binding Proteins
  • Multiprotein Complexes
  • NCOA2 protein, human
  • NR4A1 protein, human
  • Ncoa2 protein, mouse
  • Nr4a1 protein, mouse
  • Nuclear Receptor Coactivator 2
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • RNA, Small Interfering
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Recombinant Proteins
  • Retinoblastoma Protein
  • Transcription Factors
  • Pro-Opiomelanocortin