Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and SUMOylation of nuclear receptor TR2 to suppress Oct4 expression.

Détails

ID Serval
serval:BIB_B568741255C3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and SUMOylation of nuclear receptor TR2 to suppress Oct4 expression.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Gupta P., Ho P.C., Huq M.M., Ha S.G., Park S.W., Khan A.A., Tsai N.P., Wei L.N.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
12/08/2008
Peer-reviewed
Oui
Volume
105
Numéro
32
Pages
11424-11429
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
We previously reported an intricate mechanism underlying the homeostasis of Oct4 expression in normally proliferating stem cell culture of P19, mediated by SUMOylation of orphan nuclear receptor TR2. In the present study, we identify a signaling pathway initiated from the nongenomic activity of all-trans retinoic acid (atRA) to stimulate complex formation of extracellular signal-regulated kinase 2 (ERK2) with its upstream kinase, mitogen-activated protein kinase kinase (MEK). The activated ERK2 phosphorylates threonine-210 (Thr-210) of TR2, stimulating its subsequent SUMOylation. Dephosphorylated TR2 recruits coactivator PCAF and functions as an activator for its target gene Oct4. Upon phosphorylation at Thr-210, TR2 increasingly associates with promyelocytic leukemia (PML) nuclear bodies, becomes SUMOylated, and recruits corepressor RIP140 to act as a repressor for its target, Oct4. To normally proliferating P19 stem cell culture, exposure to a physiological concentration of atRA triggers a rapid nongenomic signaling cascade to suppress Oct4 gene and regulate cell proliferation.
Mots-clé
Adaptor Proteins, Signal Transducing/metabolism, Animals, Antineoplastic Agents/pharmacology, Cell Line, Embryonic Stem Cells/cytology, Embryonic Stem Cells/metabolism, Gene Expression Regulation/drug effects, Gene Expression Regulation/physiology, Homeostasis/drug effects, Homeostasis/physiology, MAP Kinase Kinase Kinases/metabolism, MAP Kinase Signaling System/drug effects, MAP Kinase Signaling System/physiology, Mice, Mitogen-Activated Protein Kinase 1/metabolism, Nuclear Proteins/metabolism, Nuclear Receptor Interacting Protein 1, Nuclear Receptor Subfamily 2, Group C, Member 1, Octamer Transcription Factor-3/biosynthesis, Phosphorylation/drug effects, Promyelocytic Leukemia Protein, Receptors, Thyroid Hormone/metabolism, Repressor Proteins/metabolism, SUMO-1 Protein/metabolism, Transcription Factors/metabolism, Tretinoin/pharmacology, Tumor Suppressor Proteins/metabolism, p300-CBP Transcription Factors/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
05/04/2019 15:40
Dernière modification de la notice
20/08/2019 15:23
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