Journal Article

A new role of NUAK1: directly phosphorylating p53 and regulating cell proliferation

Liu, Z-Y, Hou, X, Liu, C-Y, Liu, J-E, Sun, Z-Y, Liu, W

2011

Overview

It has been suggested that adenosine monophosphate-activated protein kinase (AMPK) and 12 AMPK-related kinases (ARK), including novel (nua) kinase family 1 (NUAK1), are activated by master kinase LKB1, a major tumor suppressor. Apart from evidence to suggest that NUAK1 participates in induction of tumor survival, invasion and p53-independent cellular senescence, its detailed biological functions remain unclear. Here we showed that in the presence of wild-type LKB1, NUAK1 directly interacts with and phosphorylates p53 in vitro and in vivo . The phosphorylation of p53 induced by LKB1 required the kinase activity of NUAK1 and phosphorylation of NUAK1 at Thr211 by LKB1 was essential for its kinase activity, which leads to the conclusion that LKB1 activates NUAK1 and regulates phosphorylation of p53 through the NUAK1 kinase, at least partially. LKB1/NUAK1 activation leads to cell cycle arrest at the G 1 /S border by inducing expression of p21/WAF1. Under the regulation of LKB1, NUAK1 interacts with p53 in the nucleus and binds to the p53-responsive element of p21/WAF1 promoter. These findings have highlighted a novel role for NUAK1 in LKB1-related signaling pathways; NUAK1 can regulate cell proliferation and exert tumor suppression through direct interaction with p53.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/136/2091 / 631/67/581 / 631/80/86 / Adenosine kinase / AMP / Apoptosis / Biological and medical sciences / Cell activation / Cell Biology / Cell cycle / Cell Cycle - genetics / Cell Cycle - physiology / Cell growth / Cell Nucleus - genetics / Cell Nucleus - metabolism / Cell physiology / Cell Proliferation / Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes / Cells, Cultured / Cyclin-dependent kinase inhibitor p21 / Cyclin-Dependent Kinase Inhibitor p21 - genetics / Cyclin-Dependent Kinase Inhibitor p21 - metabolism / Cyclin-Dependent Kinase Inhibitor p21 - physiology / Fundamental and applied biological sciences. Psychology / Gene expression / Genes, Tumor Suppressor - physiology / Genetic aspects / HeLa Cells / Human Genetics / Humans / Internal Medicine / Kinases / LKB1 protein / Medicine / Medicine & Public Health / Molecular and cellular biology / Neoplasms - genetics / Neoplasms - metabolism / Oncology / original-article / p53 Protein / Phosphorylation / Physiological aspects / Promoter Regions, Genetic / Protein Binding - physiology / Protein kinase / Protein Kinases - genetics / Protein Kinases - metabolism / Protein Kinases - physiology / Regulatory sequences / Repressor Proteins - genetics / Repressor Proteins - metabolism / Repressor Proteins - physiology / Senescence / Signal transduction / Signal Transduction - genetics / Signal Transduction - physiology / Tumor proteins / Tumor suppressor genes / Tumor Suppressor Protein p53 - metabolism / Tumors