期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 285, 期 47, 页码 36857-36864出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.144477
关键词
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资金
- National Natural Science Foundation of China [30171035, 30770470, 30900235]
- Zhejiang Provincial Natural Science Foundation of China [Y2090095]
- China Postdoctoral Science Foundation [20080430209, 200902638]
- Program for New Century Excellent Talents in University
- Ministry of Education [NCET-05-0521]
- Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents
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.
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