Skip Navigation



Carcinogenesis Advance Access published online on July 7, 2004
Carcinogenesis, doi:10.1093/carcin/bgh222
© 2004 by Oxford University Press
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
25/11/2083    most recent
bgh222v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Tan, E.
Right arrow Articles by Yeoh, G. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tan, E.
Right arrow Articles by Yeoh, G. C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received March 16, 2004
Revised May 31, 2004
Accepted June 22, 2004

CANCER BIOLOGY

Histone H4 histidine kinase displays the expression pattern of a liver oncodevelopmental marker

Eiling Tan 1, Paul G. Besant 2, Xin Lin Zu 1, Christoph W. Turck 3, Marie A. Bogoyevitch 1, Seng Gee Lim 4, Paul V. Attwood 1, George C. Yeoh 2*

1 Biochemistry and Molecular Biology, School of Biomedical and Chemical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia
2 Biochemistry and Molecular Biology, School of Biomedical and Chemical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009 Australia; Laboratory for Cancer Medicine, The UWA Centre for Medical Research, West Australian Institute for Medical Research, Level 5, MRF Building, 50 Murray Street, Perth, WA 6000, Australia
3 Max-Planck Institute of Psychiatry, Molecular, Cellular, Clinical Proteomics, Kraepelinstr. 2, D-80804 Munich, Germany
4 Division of Gastroenterology, Department of Medicine, National University Hospital, 5 Lower Kent Ridge Rd, Singapore 119074

* To whom correspondence should be addressed. E-mail: yeoh{at}cyllene.uwa.edu.au.


  Abstract

Protein phosphorylation is a vital process in the regulation of mammalian cell division and the protein kinases that catalyze the phosphorylation of proteins on serine, threonine and tyrosine residues have been well characterised. In contrast, little is known about the kinases involved in protein histidine phosphorylation which have been described in various mammalian cells that are highly proliferative. Histone H4 histidine kinase (HHK) activity is highly active in regenerating rat liver. Using a novel and specific assay, we demonstrate that it is active in human fetal liver, essentially absent in adult liver and highly expressed in liver tumors. "Normal" liver surrounding the HCC contains low to undetectable levels of HHK. In a rodent model of chronic liver injury that leads to HCC, its activity is induced. Two lines of evidence suggest that liver progenitor (oval) cells which populate the liver at early stages following induction of liver damage are responsible for the increased activity. Purified oval cells, as well as cell lines established from primary cultures of oval cells express high levels of HHK. We propose that the pattern of expression of histone H4 histidine kinase activity justifies its classification as an oncodevelopmental marker and suggest it may be useful as a diagnostic marker for hepatocellular carcinoma as well for identifying preneoplastic lesions.

Keywords: histone H4 histidine kinase; hepatocellular carcinoma; cellular proliferation; progenitor cells; oncodevelopmental marker.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 CarcinogenesisHome page
B. Knight, B. B. Yeap, G. C. Yeoh, and J. K. Olynyk
Inhibition of adult liver progenitor (oval) cell growth and viability by an agonist of the peroxisome proliferator activated receptor (PPAR) family member {gamma}, but not {alpha} or {delta}
Carcinogenesis, October 1, 2005; 26(10): 1782 - 1792.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.