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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Caco-2 Cells
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Cell Line
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Humans
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Kinetics
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L Cells
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Mice
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Models, Biological
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Multiprotein Complexes
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Nuclear Receptor Coactivator 2
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Pro-Opiomelanocortin / genetics
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Promoter Regions, Genetic
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Protein Structure, Tertiary
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RNA, Small Interfering / genetics
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Receptors, Cytoplasmic and Nuclear / chemistry
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Receptors, Steroid / chemistry
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Receptors, Steroid / genetics
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Receptors, Steroid / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Retinoblastoma Protein / chemistry
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Retinoblastoma Protein / genetics
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Retinoblastoma Protein / metabolism*
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic
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Transfection
Substances
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DNA-Binding Proteins
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Multiprotein Complexes
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NCOA2 protein, human
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NR4A1 protein, human
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Ncoa2 protein, mouse
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Nr4a1 protein, mouse
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Nuclear Receptor Coactivator 2
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Nuclear Receptor Subfamily 4, Group A, Member 1
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RNA, Small Interfering
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid
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Recombinant Proteins
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Retinoblastoma Protein
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Transcription Factors
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Pro-Opiomelanocortin