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

Byles, Vanessa; Chmilewski, Laura K.; Wang, Joyce; Zhu, Lijia; Forman, Lora W.; Faller, Douglas V.; Dai, Yan

doi:10.7150/ijbs.6.599

Theranostics

International Journal of Medical Sciences

Nanotheranostics

Journal of Cancer

Journal of Genomics

open access Global reach, higher impact

Full Text | PDF

Int J Biol Sci 2010; 6(6):599-612. doi:10.7150/ijbs.6.599 This issue Cite

Research Paper

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

Vanessa Byles, Laura K. Chmilewski, Joyce Wang, Lijia Zhu, Lora W. Forman, Douglas V. Faller, Yan Dai^✉

Cancer Research Center and Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.

Citation:

Byles V, Chmilewski LK, Wang J, Zhu L, Forman LW, Faller DV, Dai Y. Aberrant Cytoplasm Localization and Protein Stability of SIRT1 is Regulated by PI3K/IGF-1R Signaling in Human Cancer Cells. Int J Biol Sci 2010; 6(6):599-612. doi:10.7150/ijbs.6.599. https://www.ijbs.com/v06p0599.htm

Other styles

Abstract

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 normal cells, but is predominantly localized in the cytoplasm of the cancer / transformed 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.

Keywords: SIRT1, cytoplasm localization, protein stability, cancer cells, PI3K/IGF-1R

Citation styles

APA

Byles, V., Chmilewski, L.K., Wang, J., Zhu, L., Forman, L.W., Faller, D.V., Dai, Y. (2010). Aberrant Cytoplasm Localization and Protein Stability of SIRT1 is Regulated by PI3K/IGF-1R Signaling in Human Cancer Cells. International Journal of Biological Sciences, 6(6), 599-612. https://doi.org/10.7150/ijbs.6.599.

ACS

Byles, V.; Chmilewski, L.K.; Wang, J.; Zhu, L.; Forman, L.W.; Faller, D.V.; Dai, Y. Aberrant Cytoplasm Localization and Protein Stability of SIRT1 is Regulated by PI3K/IGF-1R Signaling in Human Cancer Cells. Int. J. Biol. Sci. 2010, 6 (6), 599-612. DOI: 10.7150/ijbs.6.599.

NLM

CSE

Byles V, Chmilewski LK, Wang J, Zhu L, Forman LW, Faller DV, Dai Y. 2010. Aberrant Cytoplasm Localization and Protein Stability of SIRT1 is Regulated by PI3K/IGF-1R Signaling in Human Cancer Cells. Int J Biol Sci. 6(6):599-612.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.