title: Citron kinase is a cell cycle-dependent, nuclear protein required for G2/M transition of hepatocytes.
abstract: Citron Kinase (Citron-K) is a cell cycle-dependent protein regulating the G(2)/M transition in hepatocytes. Synchronization studies demonstrated that expression of the Citron-K protein starts at the late S and/or the early G(2) phase after that of cyclin B1. Expression of Citron-K is developmentally regulated. Levels of Citron-K mRNA and protein are highest in embryonic liver and gradually decrease after birth. Citron-K exists in interphase nuclei and begins to disperse into the cytoplasm at prophase. It concentrates at the cleavage furrow and midbody during anaphase, telophase, and cytokinesis, implicating a role in the control of cytokinesis. However, studies with knockouts show that Citron-K is not essential for cytokinesis in hepatocytes. Instead, loss of Citron-K causes a significant increase of G(2) tetraploid nuclei in one-week-old rat and mouse liver. In addition, Citron-K deficiency triggers apoptosis in a small subset of embryonic liver cells. In summary, our data demonstrate that Citron-K has a distinct cell cycle-dependent expression pattern and cellular localization as a downstream target of Rho-GTPase and functions in the control of G(2)/M transition in the hepatocyte cell cycle.
authors.affiliation: Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, 27599, USA.
authors.forename: Huifei
authors.initials: H
authors.lastname: Liu
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Di Cunto
authors.forename: Sara
authors.initials: S
authors.lastname: Imarisio
authors.forename: Lola M
authors.initials: LM
authors.lastname: Reid
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D022781:Hepatocytes / Q000166:cytology* / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000473:pathology; D008297:Male; D008677:Metaphase; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010477:Perfusion; D011233:Precipitin Tests; D011418:Prophase; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C115635:citron-kinase; D017346:Protein Serine-Threonine Kinases