Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/11282
Share/Export:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Title

Proteolysis of the tumour suppressor hDlg in response to osmotic stress is mediated by caspases and independent of phosphorylation

AuthorsIñesta-Vaquera, Francisco A.; Centeno, Francisco; Reino, Paloma del; Sabio, Guadalupe; Mark, Peggie; Cuenda, Ana
KeywordsApoptosis
Human disc-large
Osmotic Shock
p38-mitogen
Issue DateJan-2009
PublisherBlackwell Publishing
CitationFEBS Journal 2009, 276 : 387-400
AbstractHuman disc-large (hDlg) is a scaffold protein critical for the maintenance of cell polarity and adhesion. hDlg is a component of the p38c MAP kinase pathway, which is important for the adaptation of mammalian cells to changes in environmental osmolarity. Here we report a strong decrease in the levels of hDlg protein in the human epithelial cell line HeLa when exposed to osmotic shock. This is independent of the phosphorylation state of hDlg, is prevented by preincubating the cell with the caspase inhibitor z-VAD and is part of the apoptotic process triggered by cellular stress. Although, both caspase 3 and caspase 6 are strongly activated by osmotic shock, the time course of caspase 6 activation parallels hDlg degradation, suggesting that this caspase may be responsible for the proteolysis. Mutating hDlg Asp747 to Ala abolishes caspase-induced cleavage, but does not affect the early stage of apoptosis or cell attachment. Our findings show that osmotic stress triggers hDlg degradation through a mechanism different from the one mediated by proteasomes, and we identify hDlg as a caspase substrate during the apoptotic process, although its proteolysis may not be implicated in the progression of early apoptosis.
Publisher version (URL)http://dx.doi.org/10.1111/j.1742-4658.2008.06783.x
URIhttp://hdl.handle.net/10261/11282
DOI10.1111/j.1742-4658.2008.06783.x
ISSN1742-464X
Appears in Collections:(CNB) Artículos

Show full item record
Review this work

SCOPUSTM   
Citations

6
checked on May 15, 2022

WEB OF SCIENCETM
Citations

6
checked on May 17, 2022

Page view(s)

286
checked on May 20, 2022

Google ScholarTM

Check

Altmetric

Dimensions


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.