Increased Levels of a Unique Post-Translationally Modified βIVb-Tubulin Isotype in Liver Cancer
- 21 June 2008
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 47 (28), 7572-7582
- https://doi.org/10.1021/bi8005225
Abstract
Identifying changes at the molecular level during the development of hepatocellular carcinoma is important for the detection and treatment of the disease. The characteristic structural reorganization of preneoplastic cells may involve changes in the microtubule cytoskeleton. Microtubules are dynamic protein polymers that play an essential role in cell division, maintenance of cell shape, vesicle transport, and motility. They are comprised of multiple isotypes of α- and β-tubulin. Changes in the levels of these isotypes may affect not only microtubule stability and sensitivity to drugs but also interactions with endogenous proteins. We employed a rat liver cancer model that progresses through stages similar to those of human liver cancer, including metastasis to the lung, to identify changes in the tubulin cytoskeleton during carcinogenesis. Tubulin isotypes in both liver and lung tissue were purified and subsequently separated by isoelectric focusing electrophoresis. The C-terminal isotype-defining region from each tubulin was obtained by cyanogen bromide cleavage and identified by mass spectrometry. A novel post-translational modification of βIVb-tubulin in which two hydrophobic residues are proteolyzed from the C-terminus, thus exposing a charged glutamic acid residue, was identified. The unique form of βIVb-tubulin was quantified in the liver tissue of all carcinoma stages and found to be approximately 3-fold more abundant in nodular and tumor tissue than in control tissue. The level of this form was also found to be increased in lung tissue with liver metastasis. This modification alters the C-terminal domain of one of the most abundant β-tubulin isotypes in the liver and therefore may affect the interactions of microtubules with endogenous proteins.This publication has 47 references indexed in Scilit:
- Polyglutamylation Is a Post-translational Modification with a Broad Range of SubstratesJournal of Biological Chemistry, 2008
- MEROPS: the peptidase databaseNucleic Acids Research, 2007
- A revised nomenclature for the human and rodent α-tubulin gene familyGenomics, 2007
- Hepatocellular carcinoma pathogenesis: from genes to environmentNature Reviews Cancer, 2006
- Differential Binding Regulation of Microtubule-associated Proteins MAP1A, MAP1B, and MAP2 by Tubulin PolyglutamylationJournal of Biological Chemistry, 2001
- Probability-based protein identification by searching sequence databases using mass spectrometry dataElectrophoresis, 1999
- Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes.JCI Insight, 1997
- dbEST — database for “expressed sequence tags”Nature Genetics, 1993
- Characterization of a major brain tubulin variant which cannot be tyrosinatedBiochemistry, 1991
- Postpolymerization detyrosination of alpha-tubulin: a mechanism for subcellular differentiation of microtubules.The Journal of cell biology, 1987