SIRT3 是一种定位于线粒体的肿瘤抑制因子，在应激过程中维持线粒体的完整性和代谢。
SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress.
机构信息
Genetics of Development and Disease Branch, NIDDK, NIH, Bethesda, MD 20892, USA.
出版信息
Cancer Cell. 2010 Jan 19;17(1):41-52. doi: 10.1016/j.ccr.2009.11.023.
The sirtuin gene family (SIRT) is hypothesized to regulate the aging process and play a role in cellular repair. This work demonstrates that SIRT3(-/-) mouse embryonic fibroblasts (MEFs) exhibit abnormal mitochondrial physiology as well as increases in stress-induced superoxide levels and genomic instability. Expression of a single oncogene (Myc or Ras) in SIRT3(-/-) MEFs results in in vitro transformation and altered intracellular metabolism. Superoxide dismutase prevents transformation by a single oncogene in SIRT3(-/-) MEFs and reverses the tumor-permissive phenotype as well as stress-induced genomic instability. In addition, SIRT3(-/-) mice develop ER/PR-positive mammary tumors. Finally, human breast and other human cancer specimens exhibit reduced SIRT3 levels. These results identify SIRT3 as a genomically expressed, mitochondria-localized tumor suppressor.
Sirtuin 基因家族（SIRT）被假设可以调节衰老过程并在细胞修复中发挥作用。这项工作表明，SIRT3（-/-）小鼠胚胎成纤维细胞（MEF）表现出异常的线粒体生理学，以及应激诱导的超氧化物水平增加和基因组不稳定性。在 SIRT3（-/-）MEF 中表达单个致癌基因（Myc 或 Ras）会导致体外转化和细胞内代谢的改变。超氧化物歧化酶可防止 SIRT3（-/-）MEF 中单个致癌基因的转化，并逆转肿瘤允许表型以及应激诱导的基因组不稳定性。此外，SIRT3（-/-）小鼠会发展出 ER/PR 阳性的乳腺肿瘤。最后，人类乳腺和其他人类癌症标本显示 SIRT3 水平降低。这些结果表明 SIRT3 是一种具有基因组表达和线粒体定位的肿瘤抑制因子。
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