QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 15, Issue 7, 3123-3131, July 2004

This Article Full Text Full Text (PDF) All Versions of this Article: E04-01-0060v1 15/7/3123    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bhattacharya, R. Articles by Cabral, F. Search for Related Content PubMed PubMed Citation Articles by Bhattacharya, R. Articles by Cabral, F.

A Ubiquitous -tubulin Disrupts Microtubule Assembly and Inhibits Cell Proliferation

Department of Integrative Biology and Pharmacology, The University of Texas Medical School, Houston, Texas 77030

Submitted January 23, 2004; Revised March 22, 2004; Accepted April 16, 2004
Monitoring Editor: Ted Salmon

Vertebrate tubulin is encoded by a multigene family that produces distinct gene products, or isotypes, of both the - and -tubulin subunits. The isotype sequences are conserved across species supporting the hypothesis that different isotypes subserve different functions. To date, however, most studies have demonstrated that tubulin isotypes are freely interchangeable and coassemble into all classes of microtubules. We now report that, in contrast to other isotypes, overexpression of a mouse class V -tubulin cDNA in mammalian cells produces a strong, dose-dependent disruption of microtubule organization, increased microtubule fragmentation, and a concomitant reduction in cellular microtubule polymer levels. These changes also disrupt mitotic spindle assembly and block cell proliferation. Consistent with diminished microtubule assembly, there is an increased tolerance for the microtubule stabilizing drug, paclitaxel, which is able to reverse many of the effects of class V -tubulin overexpression. Moreover, transfected cells selected in paclitaxel exhibit increased expression of class V -tubulin, indicating that this isotype is responsible for the drug resistance. The results show that class V -tubulin is functionally distinct from other tubulin isotypes and imparts unique properties on the microtubules into which it incorporates.

Abbreviations used: CHO, Chinese hamster ovary; MTB, microtubule buffer; tet, tetracycline.

^* Corresponding author. E-mail address: fcabral{at}uth.tmc.edu.

This article has been cited by other articles:

				D. L. Sackett, L. Ozbun, E. Zudaire, L. Wessner, J. M. Chirgwin, F. Cuttitta, and A. Martinez Intracellular Proadrenomedullin-Derived Peptides Decorate the Microtubules and Contribute to Cytoskeleton Function Endocrinology, June 1, 2008; 149(6): 2888 - 2898. [Abstract] [Full Text] [PDF]

				S. Yin, F. Cabral, and S. Veeraraghavan Amino acid substitutions at proline 220 of {beta}-tubulin confer resistance to paclitaxel and colcemid Mol. Cancer Ther., October 1, 2007; 6(10): 2798 - 2806. [Abstract] [Full Text] [PDF]

				H. Yang and F. Cabral Heightened Sensitivity to Paclitaxel in Class IVa beta-Tubulin-transfected Cells Is Lost as Expression Increases J. Biol. Chem., September 14, 2007; 282(37): 27058 - 27066. [Abstract] [Full Text] [PDF]

				M. Hari, F. Loganzo, T. Annable, X. Tan, S. Musto, D. B. Morilla, J. H. Nettles, J. P. Snyder, and L. M. Greenberger Paclitaxel-resistant cells have a mutation in the paclitaxel-binding region of {beta}-tubulin (Asp26Glu) and less stable microtubules. Mol. Cancer Ther., February 1, 2006; 5(2): 270 - 278. [Abstract] [Full Text] [PDF]

				K. J. Evans, E. R. Gomes, S. M. Reisenweber, G. G. Gundersen, and B. P. Lauring Linking axonal degeneration to microtubule remodeling by Spastin-mediated microtubule severing J. Cell Biol., February 14, 2005; 168(4): 599 - 606. [Abstract] [Full Text] [PDF]