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

Details

Serval ID
serval:BIB_B568741255C3
Type
Article: article from journal or magazin.
Collection
Publications
Title
Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and SUMOylation of nuclear receptor TR2 to suppress Oct4 expression.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(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
Publication state
Published
Issued date
12/08/2008
Peer-reviewed
Oui
Volume
105
Number
32
Pages
11424-11429
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
05/04/2019 15:40
Last modification date
20/08/2019 15:23
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