Document Detail


Hsp27 protects adenocarcinoma cells from UV-induced apoptosis by Akt and p21-dependent pathways of survival.
MedLine Citation:
PMID:  20858736     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ragu Kanagasabai; Krishnamurthy Karthikeyan; Kaushik Vedam; Wang Qien; Qianzheng Zhu; Govindasamy Ilangovan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-09-21
Journal Detail:
Title:  Molecular cancer research : MCR     Volume:  8     ISSN:  1557-3125     ISO Abbreviation:  Mol. Cancer Res.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-11-04     Completed Date:  2011-09-13     Revised Date:  2012-04-27    
Medline Journal Info:
Nlm Unique ID:  101150042     Medline TA:  Mol Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1399-412     Citation Subset:  IM    
Affiliation:
Division of Cardiovascular Medicine, Davis Heartand Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / metabolism*,  pathology*
Apoptosis / physiology*,  radiation effects
Cell Line, Tumor
Cell Survival / genetics,  radiation effects
Cyclin-Dependent Kinase Inhibitor p21 / physiology*,  radiation effects
Cytoprotection / physiology*,  radiation effects
DNA Damage / radiation effects
HSP27 Heat-Shock Proteins / physiology*,  radiation effects
Humans
Hydrolysis / radiation effects
Phosphorylation / physiology,  radiation effects
Protein Stability / radiation effects
Protein Transport / genetics,  radiation effects
Proto-Oncogene Proteins c-akt / physiology*,  radiation effects
Signal Transduction / genetics,  radiation effects
Tumor Suppressor Protein p53 / genetics,  metabolism,  radiation effects
Ultraviolet Rays* / adverse effects
Grant Support
ID/Acronym/Agency:
R01 HL078796-01A2/HL/NHLBI NIH HHS; R21 EB004658/EB/NIBIB NIH HHS; R21 EB004658-02/EB/NIBIB NIH HHS; R21 HL094881-01A2/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p21; 0/HSP27 Heat-Shock Proteins; 0/HSPB1 protein, human; 0/Tumor Suppressor Protein p53; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
Comments/Corrections

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