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AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells

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AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells. / Lee, Chi-Wai; Wong, Leo Lap-Yan; Tse, Edith Yuk-Ting; Liu, Heong-Fai; Leong, Veronica Yee-Law; Lee, Joyce Man-Fong; Hardie, D.Grahame; Ng, Irene Oi-Ling; Ching, Yick-Pang.

In: Cancer Research, Vol. 72, No. 17, 2012, p. 4394-4404.

Research output: Contribution to journalArticle

Harvard

Lee, C-W, Wong, LL-Y, Tse, EY-T, Liu, H-F, Leong, VY-L, Lee, JM-F, Hardie, DG, Ng, IO-L & Ching, Y-P 2012, 'AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells' Cancer Research, vol 72, no. 17, pp. 4394-4404., 10.1158/0008-5472.CAN-12-0429

APA

Lee, C-W., Wong, L. L-Y., Tse, E. Y-T., Liu, H-F., Leong, V. Y-L., Lee, J. M-F., ... Ching, Y-P. (2012). AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells. Cancer Research, 72(17), 4394-4404. 10.1158/0008-5472.CAN-12-0429

Vancouver

Lee C-W, Wong LL-Y, Tse EY-T, Liu H-F, Leong VY-L, Lee JM-F et al. AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells. Cancer Research. 2012;72(17):4394-4404. Available from: 10.1158/0008-5472.CAN-12-0429

Author

Lee, Chi-Wai; Wong, Leo Lap-Yan; Tse, Edith Yuk-Ting; Liu, Heong-Fai; Leong, Veronica Yee-Law; Lee, Joyce Man-Fong; Hardie, D.Grahame; Ng, Irene Oi-Ling; Ching, Yick-Pang / AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells.

In: Cancer Research, Vol. 72, No. 17, 2012, p. 4394-4404.

Research output: Contribution to journalArticle

Bibtex - Download

@article{5fe233a72c0a4de6ac41d708f59a5743,
title = "AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells",
author = "Chi-Wai Lee and Wong, {Leo Lap-Yan} and Tse, {Edith Yuk-Ting} and Heong-Fai Liu and Leong, {Veronica Yee-Law} and Lee, {Joyce Man-Fong} and D.Grahame Hardie and Ng, {Irene Oi-Ling} and Yick-Pang Ching",
year = "2012",
doi = "10.1158/0008-5472.CAN-12-0429",
volume = "72",
number = "17",
pages = "4394--4404",
journal = "Cancer Research",
issn = "0008-5472",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells

A1 - Lee,Chi-Wai

A1 - Wong,Leo Lap-Yan

A1 - Tse,Edith Yuk-Ting

A1 - Liu,Heong-Fai

A1 - Leong,Veronica Yee-Law

A1 - Lee,Joyce Man-Fong

A1 - Hardie,D.Grahame

A1 - Ng,Irene Oi-Ling

A1 - Ching,Yick-Pang

AU - Lee,Chi-Wai

AU - Wong,Leo Lap-Yan

AU - Tse,Edith Yuk-Ting

AU - Liu,Heong-Fai

AU - Leong,Veronica Yee-Law

AU - Lee,Joyce Man-Fong

AU - Hardie,D.Grahame

AU - Ng,Irene Oi-Ling

AU - Ching,Yick-Pang

PY - 2012

Y1 - 2012

N2 - AMP-activated protein kinase (AMPK), a biologic sensor for cellular energy status, has been shown to act upstream and downstream of known tumor suppressors. However, whether AMPK itself plays a tumor suppressor role in cancer remains unclear. Here, we found that the a2 catalytic subunit isoform of AMPK is significantly downregulated in hepatocellular carcinoma (HCC). Clinicopathologic analysis revealed that underexpression of AMPK-a2 was statistically associated with an undifferentiated cellular phenotype and poor patient prognosis. Loss of AMPK-a2 in HCC cells rendered them more tumorigenic than control cells both in vitro and in vivo. Mechanistically, ectopic expression of AMPK enhanced the acetylation and stability of p53 in HCC cells. The p53 deacetylase, SIRT1, was phosphorylated and inactivated by AMPK at Thr344, promoting p53 acetylation and apoptosis of HCC cells. Taken together, our findings suggest that underexpression of AMPK is frequently observed in HCC, and that inactivation of AMPK promotes hepatocarcinogenesis by destabilizing p53 in a SIRT1-dependent manner. ©2012 AACR.

AB - AMP-activated protein kinase (AMPK), a biologic sensor for cellular energy status, has been shown to act upstream and downstream of known tumor suppressors. However, whether AMPK itself plays a tumor suppressor role in cancer remains unclear. Here, we found that the a2 catalytic subunit isoform of AMPK is significantly downregulated in hepatocellular carcinoma (HCC). Clinicopathologic analysis revealed that underexpression of AMPK-a2 was statistically associated with an undifferentiated cellular phenotype and poor patient prognosis. Loss of AMPK-a2 in HCC cells rendered them more tumorigenic than control cells both in vitro and in vivo. Mechanistically, ectopic expression of AMPK enhanced the acetylation and stability of p53 in HCC cells. The p53 deacetylase, SIRT1, was phosphorylated and inactivated by AMPK at Thr344, promoting p53 acetylation and apoptosis of HCC cells. Taken together, our findings suggest that underexpression of AMPK is frequently observed in HCC, and that inactivation of AMPK promotes hepatocarcinogenesis by destabilizing p53 in a SIRT1-dependent manner. ©2012 AACR.

UR - http://www.scopus.com/inward/record.url?scp=84865793242&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-12-0429

DO - 10.1158/0008-5472.CAN-12-0429

M1 - Article

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 17

VL - 72

SP - 4394

EP - 4404

ER -

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