Cited by 151Retinoids in leukemia and cellular processesPeroxisome Proliferator-Activated ReceptorsNuclear Receptors and Signaling

Phosphorylation by p38MAPK and recruitment of SUG‐1 are required for RA‐induced RARγ degradation and transactivation

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Giannì, Maurizio, Bauer, Annie, Garattini, Enrico, Chambon, Pierre, Rochette‐Egly, Cécile·2002·The EMBO Journal

Abstract

The nuclear retinoic acid receptor RAR gamma 2 undergoes proteasome-dependent degradation upon ligand binding. Here we provide evidence that the domains that signal proteasome-mediated degradation overlap with those that activate transcription, i.e. the activation domains AF-1 and AF-2. The AF-1 domain signals RAR gamma 2 degradation through its phosphorylation by p38MAPK in response to RA. The AF-2 domain acts via the recruitment of SUG-1, which belongs to the 19S regulatory subunit of the 26S proteasome. Blocking RAR gamma 2 degradation through inhibition of either the p38MAPK pathway or the 26S proteasome function impairs its RA-induced transactivation activity. Thus, the turnover of RAR gamma 2 is linked to transactivation.

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Crossref · 10.1093/emboj/cdf374

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57 of 57 references verified0 citation errors · 0 not checkable

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  • RARs are also degraded by the ubiquitin-proteasome system, through the recruitment of TRIP1/SUG-1, which is a subunit of the 19S regulatory subcomplex of the proteasome with an ATPase activity.

    “RARs are also degraded by the ubiquitin-proteasome system, through the recruitment of TRIP1/SUG-1, which is a subunit of the 19S regulatory subcomplex of the proteasome with an ATPase activity ( 110-112 ).”
  • RA activates p38MAPK in fibroblasts, mouse embryo carcinoma cells, mammary breast tumor cells, and leukemia cells.

    “RA activates the p38 mitogen-activated protein kinase (p38MAPK) in fi broblasts, mouse embryo carcinoma cells, mammary breast tumor cells, and leukemia cells ( 96,111,114,115 ).”
  • At the end of the RA signal, the proteasomal degradation of RARγ depends on phosphorylation by p38MAPK of an additional serine residue located in the NTD.

    “At the end of the RA signal, the proteasomal degradation of RAR ␥ has been shown to depend on the phosphorylation by p38MAPK of an additional serine residue located in the NTD ( 110, 111 ).”

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Authors
Giannì, M., Bauer, A., Garattini, E., Chambon, P., & Rochette‐Egly, C.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Mario Negri Institute for Pharmacological Research (IT)
Corresponding author
Rochette‐Egly, Cécile
Venue
The EMBO Journal
Published
2002-07-15
Volume
21
Issue
14
Pages
3760-3769
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W2004745065
Cited by
151
References
58
Citations by year
2026: 2 · 2025: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2019: 7 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 4 · 2014: 7 · 2013: 6 · 2012: 2
FWCI
4.76
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Funders
  • Bristol-Myers Squibb
  • Association pour la Recherche sur le Cancer
  • Institut National de la Santé et de la Recherche Médicale
  • Centre National de la Recherche Scientifique
  • Fondazione Italiana per la Ricerca sul Cancro
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
retinoic acid receptor gamma, p38 MAPK, proteasomal degradation, 26S proteasome, protein phosphorylation, receptor turnover
MeSH terms
ATPases Associated with Diverse Cellular Activities, Retinoic Acid Receptor gamma, Animals, Carrier Proteins, Cysteine Endopeptidases, Ligands, Multienzyme Complexes, Phosphorylation, Transcription Factors, Tretinoin, Transcriptional Activation, Receptors, Retinoic Acid, COS Cells, Mitogen-Activated Protein Kinases, Ubiquitin, Proteasome Endopeptidase Complex, Intracellular Signaling Peptides and Proteins, p38 Mitogen-Activated Protein Kinases, Adaptor Proteins, Signal Transducing, LIM Domain Proteins

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