Aberrant Cytoplasm Localization and Protein Stability of SIRT1 is Regulated by PI3K/IGF-1R Signaling in Human Cancer Cells

作者：Byles Vanessa; Chmilewski Laura K; Wang Joyce; Zhu Lijia; Forman Lora W; Faller Douglas V; Dai Yan^*

来源：International Journal of Biological Sciences, 2010, 6(6): 599-612.

DOI：10.7150/ijbs.6.599

• SIRT1
• cytoplasm localization
• protein stability
• cancer cells
• PI3K/IGF-1R

SIRT1, an NAD-dependent histone/protein deacetylase, has classically been thought of as a nuclear protein. In this study, we demonstrate that SIRT1 is mainly localized in the nucleus of nor mal cells, but is predominantly localized in the cytoplasm of the cancer/transfor med cells we tested. We found this predominant cytoplasmic localization of SIRT1 is regulated by elevated mitotic activity and PI3K/IGF-1R signaling in cancer cells. We show that aberrant cytoplasmic localization of SIRT1 is due to increased protein stability and is regulated by PI3K/IGF-1R signaling. In addition, we determined that SIRT1 is required for PI3K-mediated cancer cell growth. Our study represents the first identification that aberrant cytoplasm localization is one of the specific alternations to SIRT1 that occur in cancer cells, and PI3K/IGF-1R signaling plays an important role in the regulation of cytoplasmic SIRT1 stability. Our findings suggest that the over-expressed cytoplasmic SIRT1 in cancer cells may greatly contribute to its cancer-specific function by working downstream of the PI3K/IGF-1R signaling pathway.

• 出版日期2010