Molecular structure and differential function of choline kinases CHKα and CHKβ in musculoskeletal system and cancer

Xi Chen; Heng Qiu; Chao Wang; Yu Yuan; Jennifer Tickner; Jiake Xu; Jun Zou

doi:10.1016/j.cytogfr.2016.10.002

Molecular structure and differential function of choline kinases CHKα and CHKβ in musculoskeletal system and cancer

Cytokine Growth Factor Rev. 2017 Feb:33:65-72. doi: 10.1016/j.cytogfr.2016.10.002. Epub 2016 Oct 8.

Authors

Xi Chen¹, Heng Qiu², Chao Wang², Yu Yuan³, Jennifer Tickner², Jiake Xu⁴, Jun Zou⁵

Affiliations

¹ School of Kinesiology, Shanghai University of Sport, Shanghai 200438, PR China; School of Sports Science, Wenzhou Medical University, Wenzhou, 325035, PR China; School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, 6009, Australia.
² School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, 6009, Australia.
³ School of Kinesiology, Shanghai University of Sport, Shanghai 200438, PR China; School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, 6009, Australia.
⁴ School of Kinesiology, Shanghai University of Sport, Shanghai 200438, PR China; School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, 6009, Australia. Electronic address: jiake.xu@uwa.edu.au.
⁵ School of Kinesiology, Shanghai University of Sport, Shanghai 200438, PR China. Electronic address: junzou@sus.edu.cn.

PMID: 27769579
DOI: 10.1016/j.cytogfr.2016.10.002

Abstract

Choline, a hydrophilic cation, has versatile physiological roles throughout the body, including cholinergic neurotransmission, memory consolidation and membrane biosynthesis and metabolism. Choline kinases possess enzyme activity that catalyses the conversion of choline to phosphocholine, which is further converted to cytidine diphosphate-coline (CDP-choline) in the biosynthesis of phosphatidylcholine (PC). PC is a major constituent of the phospholipid bilayer which constitutes the eukaryotic cell membrane, and regulates cell signal transduction. Choline Kinase consists of three isoforms, CHKα1, CHKα2 and CHKβ, encoded by two separate genes (CHKA(Human)/Chka(Mouse) and CHKB(Human)/Chkb(Mouse)). Both isoforms have similar structures and enzyme activity, but display some distinct molecular structural domains and differential tissue expression patterns. Whilst Choline Kinase was discovered in early 1950, its pivotal role in the development of muscular dystrophy, bone deformities, and cancer has only recently been identified. CHKα has been proposed as a cancer biomarker and its inhibition as an anti-cancer therapy. In contrast, restoration of CHKβ deficiency through CDP-choline supplements like citicoline may be beneficial for the treatment of muscular dystrophy, bone metabolic diseases, and cognitive conditions. The molecular structure and expression pattern of Choline Kinase, the differential roles of Choline Kinase isoforms and their potential as novel therapeutic targets for muscular dystrophy, bone deformities, cognitive conditions and cancer are discussed.

Keywords: CHKα; CHKβ; Cancer; Choline kinase; Musculoskeletal system.

Publication types

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

MeSH terms

Animals
Biomarkers, Tumor
Choline Kinase / chemistry*
Choline Kinase / deficiency
Choline Kinase / genetics
Choline Kinase / metabolism*
Humans
Metabolic Diseases / drug therapy
Mice
Molecular Structure
Muscular Dystrophies / drug therapy
Musculoskeletal System / enzymology*
Musculoskeletal System / physiopathology
Neoplasms / enzymology*
Neoplasms / physiopathology

Substances

Biomarkers, Tumor
CHKA protein, human
CHKB protein, human
Choline Kinase