2024-03-29T15:06:06Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/90072021-12-27T16:43:35Zcom_10261_86com_10261_1col_10261_339
Glyceraldehyde-3-phosphate dehydrogenase regulates endothelin-1 expression by a novel, redox-sensitive mechanism involving mRNA stability
Rodríguez-Pascual, Fernando
Redondo-Horcajo, Mariano
Magán-Marchal, Noemi
Lagares, David
Martínez-Ruiz, Antonio
Kleinert, Hartmut
Lamas Peláez, Santiago
Endothelin-1 (ET-1)
mRNA stability
Glyceraldehyde-3'-phosphate dehydrogenase (GAPDH)
17 pages.-- PMID: 18809573 [PubMed].-- Printed version published on Dec 2008.
The regulation of the synthesis of the endothelial-derived vasoconstrictor endothelin-1 (ET-1) is a complex process encompassing transcriptional as well as mRNA stability mechanisms. We have described recently the existence of a mechanism for the control of ET-1 expression based on the mRNA-destabilizing capacity of specific cytosolic proteins through interaction with AU-rich elements (AREs) present in the 3'-UTR of the gene. We now identify glyceraldehyde-3'-phosphate dehydrogenase (GAPDH) as a protein which binds to the AREs and is responsible for its destabilization. Oxidant stress alters the binding of GAPDH to the mRNA and its capacity to modulate ET-1 expression, a phenomenon occurring through specific S-glutathionylation of the catalytically active residue Cys 152. Finally we provide data consistent with a role for GAPDH in mRNA unwinding, yielding this molecule more prone to degradation. By contrast, S-thiolated GAPDH appears unable to modify mRNA unwinding, thus facilitating enhanced stability. Taken together, these results describe a novel, redox-based mechanism regulating mRNA stability and add a new facet to the panoply of GAPDH cellular homeostatic actions.
2008-12-04T16:46:28Z
2008-12-04T16:46:28Z
2008-09-22
artículo
Molecular and Cellular Biology 28(23): 7139-7155 (2008)
0270-7306
http://hdl.handle.net/10261/9007
10.1128/MCB.01145-08
18809573
eng
http://dx.doi.org/10.1128/MCB.01145-08
closedAccess
American Society for Microbiology