Rb enhances p160/SRC coactivator-dependent activity of nuclear receptors and hormone responsiveness.
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.
Batsché
Eric
E
Laboratoire de Génétique Moléculaire, Institut de Recherches Cliniques de Montréal, Quebec, Canada.
Desroches
Julien
J
Bilodeau
Steve
S
Gauthier
Yves
Y
Drouin
Jacques
J
D000818:Animals; D001483:Base Sequence; D018938:Caco-2 Cells; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007739:L Cells; D051379:Mice; D008954:Models, Biological; D046912:Multiprotein Complexes; D051958:Nuclear Receptor Coactivator 2; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; C498001:NCOA2 protein, human; C539821:NR4A1 protein, human; C498002:Ncoa2 protein, mouse; C539818:Nr4a1 protein, mouse; D051958:Nuclear Receptor Coactivator 2; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D011333:Pro-Opiomelanocortin