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PMID:16723356

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Citation

Flajollet, S, Lefebvre, B, Rachez, C and Lefebvre, P (2006) Distinct roles of the steroid receptor coactivator 1 and of MED1 in retinoid-induced transcription and cellular differentiation. J. Biol. Chem. 281:20338-48

Abstract

Retinoic acid receptors (RARs) are the molecular relays of retinoid action on transcription, cellular differentiation and apoptosis. Transcriptional activation of retinoid-regulated promoters requires the dismissal of corepressors and the recruitment of coactivators to promoter-bound RAR. RARs recruit in vitro a plethora of coactivators whose actual contribution to retinoid-induced transcription is poorly characterized in vivo. Embryonal carcinoma P19 cells, which are highly sensitive to retinoids, were depleted from archetypical coactivators by RNAi. SRC1-deficient P19 cells showed severely compromised retinoid-induced responses, in agreement with the supposed role of SRC1 as a RAR coactivator. Unexpectedly, Med1/TRAP220/DRIP205-depleted cells exhibited an exacerbated response to retinoids, both in terms transcriptional responses and of cellular differentiation. Med1 depletion affected TFIIH and cdk9 detection at the prototypical retinoid-regulated RARbeta2 promoter, and favored a higher RNA polymerase II detection in transcribed regions of the RARbeta2 gene. Furthermore, the nature of the ligand impacted strongly on the ability of RARs to interact with a given coactivator and to activate transcription in intact cells. Thus RAR accomplishes transcriptional activation as a function of the ligand structure, by recruiting regulatory complexes which control distinct molecular events at retinoid-regulated promoters.

Links

PubMed Online version:10.1074/jbc.M603023200

Keywords

Animals; Cell Differentiation/drug effects; Cell Line, Tumor; Cloning, Molecular; Endodeoxyribonucleases/deficiency; Endodeoxyribonucleases/genetics; Endodeoxyribonucleases/physiology; Gene Deletion; Genes, Reporter; HeLa Cells; Histone Acetyltransferases; Humans; Kinetics; Luciferases/genetics; Mice; Models, Biological; Nuclear Receptor Coactivator 1; Receptors, Retinoic Acid/drug effects; Receptors, Retinoic Acid/physiology; Retinoids/pharmacology; Transcription Factors/deficiency; Transcription Factors/genetics; Transcription Factors/physiology; Transcription, Genetic/drug effects

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:RARA

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q925J9

F

Seeded From UniProt

complete

MOUSE:RABP2

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:NCOA1

enables

GO:0003713: transcription coactivator activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:NCOA1

involved_in

GO:0000435: positive regulation of transcription from RNA polymerase II promoter by galactose

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(UniProtKB:P22935)

Seeded From UniProt

complete

MOUSE:NCOA1

involved_in

GO:0043967: histone H4 acetylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NCOA1

involved_in

GO:2001141: regulation of RNA biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NCOA1

involved_in

GO:2001038: regulation of cellular response to drug

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NCOA1

involved_in

GO:0043065: positive regulation of apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NCOA1

involved_in

GO:0045666: positive regulation of neuron differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MED1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P11416

F

Seeded From UniProt

complete

MOUSE:MED1

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(UniProtKB:P22935)|has_input:(UniProtKB:P22605)

Seeded From UniProt

complete

MOUSE:MED1

enables

GO:0003714: transcription corepressor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:MED1

involved_in

GO:0043066: negative regulation of apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MED1

involved_in

GO:0042789: mRNA transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(UniProtKB:P22605)

Seeded From UniProt

complete

MOUSE:MED1

involved_in

GO:0045665: negative regulation of neuron differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:RABP2

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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