| SM22α-induced activation of p16INK4a/retinoblastoma pathway promotes cellular senescence caused by a subclinical dose of γ-radiation and doxorubicin in HepG2 cells. | |
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MedLine Citation:
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PMID: 20705054 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Smooth muscle protein 22-alpha (SM22α) is known as a transformation- and shape change-sensitive actin cross-linking protein found in smooth muscle tissue and fibroblasts; however, its functional role remains uncertain. We reported previously that SM22α overexpression confers resistance against anti-cancer drugs or radiation via induction of metallothionein (MT) isozymes in HepG2 cells. In this study, we demonstrate that SM22α overexpression leads cells to a growth arrest state and promotes cellular senescence caused by treatment with a subclinical dose of γ-radiation (0.05 and 0.1 Gy) or doxorubicin (0.01 and 0.05 μg/ml), compared to control cells. Senescence growth arrest is known to be controlled by p53 phosphorylation/p21(WAF1/Cip1) induction or p16(INK4a)/retinoblastoma protein (pRB) activation. SM22α overexpression in HepG2 cells elevated p16(INK4a) followed by pRB activation, but did not activate the p53/p21(WAF1/Cip1) pathway. Moreover, MT-1G, which is induced by SM22α overexpression, was involved in the activation of the p16(INK4a)/pRB pathway, which led to a growth arrest state and promoted cellular senescence caused by damaging agents. Our findings provide the first demonstration that SM22α modulates cellular senescence caused by damaging agents via regulation of the p16(INK4a)/pRB pathway in HepG2 cells and that these effects of SM22α are partially mediated by MT-1G. |
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Authors:
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Tae Rim Kim; Hee Min Lee; So Yong Lee; Eun Jin Kim; Kug Chan Kim; Sang Gi Paik; Eun Wie Cho; In Gyu Kim |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-10 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 400 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-13 Completed Date: 2010-10-11 Revised Date: 2011-11-10 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 100-5 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Daejeon, Republic of Korea. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antibiotics, Antineoplastic
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pharmacology Cell Aging* Cell Line, Tumor Cyclin-Dependent Kinase Inhibitor p16 / metabolism* Doxorubicin / pharmacology Gamma Rays Humans Metallothionein / genetics, metabolism* Microfilament Proteins / genetics, metabolism* Muscle Proteins / genetics, metabolism* Retinoblastoma Protein / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antineoplastic; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/MT1G protein, human; 0/Microfilament Proteins; 0/Muscle Proteins; 0/Retinoblastoma Protein; 0/transgelin; 23214-92-8/Doxorubicin; 9038-94-2/Metallothionein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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