P38MAPK-dependent phosphorylation and degradation of SRC-3/AIB1 and RARα-mediated transcription

Autor: Enrico Garattini, Claudine Gaudon, Ivan Raska, Maurizio Gianni, Emilie Gaillard, Edoardo Parrella, Elisa Agnese Nigro, Cécile Rochette-Egly
Přispěvatelé: Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2006
Předmět:
Genetics and Molecular Biology (all)
Transcription
Genetic
Receptors
Retinoic Acid
Immunology and Microbiology (all)
Cellular differentiation
Retinoic Acid
Retinoic acid
p38 Mitogen-Activated Protein Kinases
Biochemistry
Nuclear Receptor Coactivator 3
Mice
MESH: Histone Acetyltransferases
chemistry.chemical_compound
0302 clinical medicine
Transcription (biology)
Chlorocebus aethiops
Receptors
Gene expression
MESH: Animals
Phosphorylation
Histone Acetyltransferases
Oncogene Proteins
0303 health sciences
Retinoic Acid Receptor alpha
General Neuroscience
MESH: Gene Expression Regulation
MESH: COS Cells
030220 oncology & carcinogenesis
COS Cells
Coactivator
Transcription
Proto-oncogene tyrosine-protein kinase Src
MESH: Trans-Activators
Antineoplastic Agents
HL-60 Cells
Tretinoin
Biology
Article
General Biochemistry
Genetics and Molecular Biology
Cercopithecus aethiops
Nuclear receptor
Proteasome
SRC-3/AIB1
Acetyltransferases
Animals
Gene Expression Regulation
Humans
Multiprotein Complexes
Protein Processing
Post-Translational
Trans-Activators
Neuroscience (all)
Molecular Biology
Biochemistry
Genetics and Molecular Biology (all)
03 medical and health sciences
MESH: Oncogene Proteins
Genetic
MESH: HL-60 Cells
MESH: Mice
Protein Processing
030304 developmental biology
MESH: Receptors
Retinoic Acid
MESH: Tretinoin
MESH: Humans
MESH: Phosphorylation
General Immunology and Microbiology
MESH: Transcription
Genetic
Post-Translational
MESH: Acetyltransferases
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
MESH: Multiprotein Complexes
MESH: Cercopithecus aethiops
Molecular biology
MESH: p38 Mitogen-Activated Protein Kinases
chemistry
MESH: Protein Processing
Post-Translational
MESH: Antineoplastic Agents
Zdroj: EMBO Journal
EMBO Journal, EMBO Press, 2006, 25 (4), pp.739-51. ⟨10.1038/sj.emboj.7600981⟩
ISSN: 1460-2075
0261-4189
Popis: International audience; Nuclear retinoic acid (RA) receptors (RARs) activate gene expression through dynamic interactions with coregulators in coordination with the ligand and phosphorylation processes. Here we show that during RA-dependent activation of the RARalpha isotype, the p160 coactivator pCIP/ACTR/AIB-1/RAC-3/TRAM-1/SRC-3 is phosphorylated by p38MAPK. SRC-3 phosphorylation has been correlated to an initial facilitation of RARalpha-target genes activation, via the control of the dynamics of the interactions of the coactivator with RARalpha. Then, phosphorylation inhibits transcription via promoting the degradation of SRC-3. In line with this, inhibition of p38MAPK markedly enhances RARalpha-mediated transcription and RA-dependent induction of cell differentiation. SRC-3 phosphorylation and degradation occur only within the context of RARalpha complexes, suggesting that the RAR isotype defines a phosphorylation code through dictating the accessibility of the coactivator to p38MAPK. We propose a model in which RARalpha transcriptional activity is regulated by SRC-3 through coordinated events that are fine-tuned by RA and p38MAPK.
Databáze: OpenAIRE
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