Document Detail


Nucleolar follistatin promotes cancer cell survival under glucose-deprived conditions through inhibiting cellular rRNA synthesis.
MedLine Citation:
PMID:  20843798     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Solid tumor development is frequently accompanied by energy-deficient conditions such as glucose deprivation and hypoxia. Follistatin (FST), a secretory protein originally identified from ovarian follicular fluid, has been suggested to be involved in tumor development. However, whether it plays a role in cancer cell survival under energy-deprived conditions remains elusive. In this study, we demonstrated that glucose deprivation markedly enhanced the expression and nucleolar localization of FST in HeLa cells. The nucleolar localization of FST relied on its nuclear localization signal (NLS) comprising the residues 64-87. Localization of FST to the nucleolus attenuated rRNA synthesis, a key process for cellular energy homeostasis and cell survival. Overexpression of FST delayed glucose deprivation-induced apoptosis, whereas down-regulation of FST exerted the opposite effect. These functions depended on the presence of an intact NLS because the NLS-deleted mutant of FST lost the rRNA inhibition effect and the cell protective effect. Altogether, we identified a novel nucleolar function of FST, which is of importance in the modulation of cancer cell survival in response to glucose deprivation.
Authors:
Xiangwei Gao; Saisai Wei; Kairan Lai; Jinghao Sheng; Jinfeng Su; Junqiao Zhu; Haojie Dong; Hu Hu; Zhengping Xu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-15
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-15     Completed Date:  2011-02-28     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  36857-64     Citation Subset:  IM    
Affiliation:
Institute of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis*
Blotting, Northern
Blotting, Western
Cell Nucleolus / metabolism*
Chromatin Immunoprecipitation
Down-Regulation
Female
Fluorescent Antibody Technique
Follistatin / antagonists & inhibitors,  genetics,  metabolism*
Glucose / deficiency*
HeLa Cells
Humans
Nuclear Localization Signals
RNA, Messenger / genetics
RNA, Ribosomal / antagonists & inhibitors,  biosynthesis*
RNA, Small Interfering / genetics
Reverse Transcriptase Polymerase Chain Reaction
Uterine Cervical Neoplasms / metabolism,  pathology*
Chemical
Reg. No./Substance:
0/FST protein, human; 0/Follistatin; 0/Nuclear Localization Signals; 0/RNA, Messenger; 0/RNA, Ribosomal; 0/RNA, Small Interfering; 50-99-7/Glucose
Comments/Corrections

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