Increased levels of a unique post-translationally modified βIVb-tubulin isotype in liver cancer

Leah M. Miller, Anuradha Menthena, Champak Chatterjee, Pascal Verdier-Pinard, Phyllis M. Novikoff, Susan Band Horwitz, Ruth Hogue Angeletti

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)7572-7582
Number of pages11
JournalBiochemistry
Volume47
Issue number28
DOIs
StatePublished - Jul 15 2008

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Tubulin
Liver Neoplasms
Liver
Tissue
Microtubules
Cytoskeleton
Lung
Neoplasm Metastasis
Microtubule Proteins
Transport Vesicles
Cyanogen Bromide
Cell Shape
Isoelectric Focusing
Post Translational Protein Processing
Electrophoresis
Drug Interactions
Cell Division
Mass spectrometry
Rats
Tumors

ASJC Scopus subject areas

  • Biochemistry

Cite this

Miller, L. M., Menthena, A., Chatterjee, C., Verdier-Pinard, P., Novikoff, P. M., Band Horwitz, S., & Angeletti, R. H. (2008). Increased levels of a unique post-translationally modified βIVb-tubulin isotype in liver cancer. Biochemistry, 47(28), 7572-7582. https://doi.org/10.1021/bi8005225

Increased levels of a unique post-translationally modified βIVb-tubulin isotype in liver cancer. / Miller, Leah M.; Menthena, Anuradha; Chatterjee, Champak; Verdier-Pinard, Pascal; Novikoff, Phyllis M.; Band Horwitz, Susan; Angeletti, Ruth Hogue.

In: Biochemistry, Vol. 47, No. 28, 15.07.2008, p. 7572-7582.

Research output: Contribution to journalArticle

Miller, LM, Menthena, A, Chatterjee, C, Verdier-Pinard, P, Novikoff, PM, Band Horwitz, S & Angeletti, RH 2008, 'Increased levels of a unique post-translationally modified βIVb-tubulin isotype in liver cancer', Biochemistry, vol. 47, no. 28, pp. 7572-7582. https://doi.org/10.1021/bi8005225
Miller LM, Menthena A, Chatterjee C, Verdier-Pinard P, Novikoff PM, Band Horwitz S et al. Increased levels of a unique post-translationally modified βIVb-tubulin isotype in liver cancer. Biochemistry. 2008 Jul 15;47(28):7572-7582. https://doi.org/10.1021/bi8005225
Miller, Leah M. ; Menthena, Anuradha ; Chatterjee, Champak ; Verdier-Pinard, Pascal ; Novikoff, Phyllis M. ; Band Horwitz, Susan ; Angeletti, Ruth Hogue. / Increased levels of a unique post-translationally modified βIVb-tubulin isotype in liver cancer. In: Biochemistry. 2008 ; Vol. 47, No. 28. pp. 7572-7582.
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