4.3 Article Proceedings Paper

Choline kinase and its function

Journal

BIOCHEMISTRY AND CELL BIOLOGY
Volume 88, Issue 4, Pages 559-564

Publisher

CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS
DOI: 10.1139/O09-160

Keywords

choline kinase; phosphatidylcholine; embryonic lethality; muscular dystrophy; cancer

Funding

  1. Canadian Institutes of Health Research [MOP 5182] Funding Source: Medline

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Choline kinase (CK) was discovered in 1953 Progress in understanding the function of CK was slow until its purification in 1984 The subsequent cloning and expression of the cDNA led to the description of the gene structures Two genes encode choline kinase, Chka and Chkb, and 3 isoforms of the enzyme have been identified - CK alpha-1, CK alpha-2, and CK beta - and the active form of CK is a hetero- or homo-dimer. More recently, gene-disrupted mice have been described Mice that lack CK alpha die early in embryogenesis. In contrast, mice that lack CK beta survive to adulthood, but develop hindlimb muscular dystrophy and forelimb bone deformity It has been shown that this hindlimb muscular dystrophy is due to decreased biosynthesis of phosphatidylcholine and increased catabolism of phosphatidylcholine in the hindlimbs, but not the forelimbs. of mice CK and its product phosphocholine have also been implicated in development of numerous cancers Thus, a possible treatment for some kinds of cancer may involve drug inhibition of CK or targeting the expression of CK with RNA interference In the mid 1950s it was clear that CK was important for the biosynthesis of phosphatidylcholine, but no one predicted a role for CK in muscular dystrophy, bone deformities, or cancer.

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