Linked Life Data

20858736

Source:http://linkedlifedata.com/resource/pubmed/id/20858736

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2010-11-4
pubmed:abstractText
Transcriptional activation of p53 target genes, due to DNA damage, causes either apoptosis or survival by cell cycle arrest and DNA repair. However, the regulators of the choice between cell death and survival signaling have not been completely elucidated. Here, we report that human adenocarcinoma cells (MCF-7) survive UV-induced DNA damage by heat shock protein 27 (Hsp27)-assisted Akt/p21 phosphorylation/translocation. Protein levels of the p53 target genes, such as p21, Bcl-2, p38MAPK, and Akt, showed a positive correlation to Hsp27 level during 48 hours postirradiation, whereas p53 expression increased initially but started decreasing after 12 hours. Hsp27 prevented the G(1)-S phase cell cycle arrest, observed after 8 hours of post-UV irradiation, and PARP-1 cleavage was inhibited. Conversely, silencing Hsp27 enhanced G(1)-S arrest and cell death. Moreover, use of either Hsp27 or Akt small interference RNA reduced p21 phosphorylation and enhanced its retention in nuclei even after 48 hours postirradiation, resulting in enhanced cell death. Our results showed that Hsp27 expression and its direct chaperoning interaction increases Akt stability, and p21 phosphorylation and nuclear-to-cytoplasm translocation, both essential effects for the survival of UV-induced DNA-damaged cells. We conclude that the role of Hsp27 in cancer is not only for enhanced p53 proteolysis per se, rather it is also a critical determinant in p21 phosphorylation and translocation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1557-3125
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1399-412
pubmed:dateRevised
2011-10-3
pubmed:meshHeading
pubmed-meshheading:20858736-Adenocarcinoma, pubmed-meshheading:20858736-Apoptosis, pubmed-meshheading:20858736-Cell Line, Tumor, pubmed-meshheading:20858736-Cell Survival, pubmed-meshheading:20858736-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:20858736-Cytoprotection, pubmed-meshheading:20858736-DNA Damage, pubmed-meshheading:20858736-HSP27 Heat-Shock Proteins, pubmed-meshheading:20858736-Humans, pubmed-meshheading:20858736-Hydrolysis, pubmed-meshheading:20858736-Phosphorylation, pubmed-meshheading:20858736-Protein Stability, pubmed-meshheading:20858736-Protein Transport, pubmed-meshheading:20858736-Proto-Oncogene Proteins c-akt, pubmed-meshheading:20858736-Signal Transduction, pubmed-meshheading:20858736-Tumor Suppressor Protein p53, pubmed-meshheading:20858736-Ultraviolet Rays
pubmed:year
2010
pubmed:articleTitle
Hsp27 protects adenocarcinoma cells from UV-induced apoptosis by Akt and p21-dependent pathways of survival.
pubmed:affiliation
Division of Cardiovascular Medicine, Davis Heartand Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural