Posttranslational regulation of liver kinase B1 in human cancer

Lanlin Hu; Mingxin Liu; Bo Tang; Qiang Li; Bo-Syong Pan; Chuan Xu; Hui-Kuan Lin

doi:10.1016/j.jbc.2023.104570

Posttranslational regulation of liver kinase B1 in human cancer

J Biol Chem. 2023 Apr;299(4):104570. doi: 10.1016/j.jbc.2023.104570. Epub 2023 Mar 3.

Authors

Lanlin Hu¹, Mingxin Liu², Bo Tang¹, Qiang Li³, Bo-Syong Pan⁴, Chuan Xu⁵, Hui-Kuan Lin⁶

Affiliations

¹ Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China.
² Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China.
³ Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China.
⁴ Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
⁵ Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. Electronic address: xuchuan100@163.com.
⁶ Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. Electronic address: hulin@wakehealth.edu.

Abstract

Liver kinase B1 (LKB1) is a serine-threonine kinase that participates in multiple cellular and biological processes, including energy metabolism, cell polarity, cell proliferation, cell migration, and many others. LKB1 is initially identified as a germline-mutated causative gene in Peutz-Jeghers syndrome and is commonly regarded as a tumor suppressor due to frequent inactivation in a variety of cancers. LKB1 directly binds and activates its downstream kinases including the AMP-activated protein kinase (AMPK) and AMPK-related kinases by phosphorylation, which has been intensively investigated for the past decades. An increasing number of studies have uncovered the posttranslational modifications (PTMs) of LKB1 and consequent changes in its localization, activity, and interaction with substrates. The alteration in LKB1 function as a consequence of genetic mutations and aberrant upstream signaling regulation leads to tumor development and progression. Here, we review current knowledge about the mechanism of LKB1 in cancer and the contributions of PTMs, such as phosphorylation, ubiquitination, SUMOylation, acetylation, prenylation, and others, to the regulation of LKB1 function, offering new insights into the therapeutic strategies in cancer.

Keywords: AMPK; cancer therapy; liver kinase B1; posttranslational modification.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

AMP-Activated Protein Kinases* / genetics
AMP-Activated Protein Kinases* / metabolism
Humans
Liver / metabolism
Neoplasms* / enzymology
Peutz-Jeghers Syndrome / genetics
Peutz-Jeghers Syndrome / metabolism
Phosphorylation
Protein Processing, Post-Translational*
Protein Serine-Threonine Kinases / metabolism

Substances

AMP-Activated Protein Kinases
Protein Serine-Threonine Kinases
STK11 protein, human