Document Detail

Synergistic effect of retinoic acid and cytokines on the regulation of glial fibrillary acidic protein expression.
MedLine Citation:
PMID:  20876578     Owner:  NLM     Status:  MEDLINE    
Glial fibrillary acidic protein (GFAP) is the main astroglial marker during astrogliogenesis, but it is also expressed in other cell types, including neural stem cells and old neurons. Activation of the JAK/STAT pathway by the IL-6 family of cytokines is the canonical pathway regulating GFAP expression, whereas retinoic acid is thought to be the only inducer of GFAP to operate independently of this pathway. Here, we show that retinoic acid receptor α not only links retinoic acid signaling to the canonical cytokine-stimulated pathway leading to GFAP expression but that it also plays a key role in the synergistic actions of retinoic acid and cytokines on this pathway. Cytokines both potentiate retinoic acid receptor α expression and enhance its binding to DNA and to the Stat3-p300/CBP-Smad transcriptional complex, the cornerstone of the canonical pathway. PI3K is upstream to all the key events leading to the expression of GFAP. Our results give new insights about the role of retinoic acid signaling in GFAP expression.
Federico Herrera; Qi Chen; David Schubert
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Publication Detail:
Type:  Journal Article     Date:  2010-09-28
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-06     Completed Date:  2011-01-10     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  38915-22     Citation Subset:  IM    
Cellular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
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MeSH Terms
Astrocytes / cytology,  metabolism*
Brain / metabolism
Cell Differentiation
Cytokines / metabolism*
Disulfides / chemistry
Gene Expression Regulation*
Glial Fibrillary Acidic Protein / metabolism*
Hippocampus / metabolism
Interleukin-6 / metabolism
Nerve Growth Factors / metabolism
Receptors, Retinoic Acid / metabolism
Transcription, Genetic
Tretinoin / metabolism*
Reg. No./Substance:
0/Cytokines; 0/Disulfides; 0/Glial Fibrillary Acidic Protein; 0/Interleukin-6; 0/Nerve Growth Factors; 0/Receptors, Retinoic Acid; 0/retinoic acid receptor alpha; 302-79-4/Tretinoin

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