Tubulin isotypes

Ranganathan S, Benetatos CA, Colamsso PJ et al (1998) Altered beta-tubulin isotype expression in paclitaxel-resistant human prostate carcinoma cells. Br J Cancer 77 562-566... 

Sullivan, K.F. (1988). Structure and utilization of tubulin isotypes. Ann. Rev. Cell Biol. 4,687-716. 

Multiple genes exist for both a- and (3-tubulins. Tubulin isotypes differ primarily at the carboxy-terminus, the region where most post-translational modifications and MAP interactions occur. While most a- and (3-tubulin isotypes are expressed in all tissues, some are expressed preferentially in different tissues. For example, class III and IVa (3-tubulins are neuron-specific (reviewed in [3,14]). It is not known if such examples of tissue-specific... 

Kavallaris M, Kuo DY, Burkhart CA, et al. Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. J Clin Invest 1997 100(5) 1282-1293. 

Montgomery RB, Guzman J, O Rourke DM, Stahl WL. Expression of oncogenic epidermal growth factor receptor family kinases induces paclitaxel resistance and alters beta-tubulin isotype expression. J Biol Chem 2000 275 17,358-17,363. 

Lu, C., Srayko, M., and Mains, P. E. (2004). The Caenorhabditis elegans microtubule-severing complex MEI-l/MEI-2 katanin interacts differently with two superficially redundant /J-tubulin isotypes. Mol. Biol. Cell 15, 142-150. 

Besides P-gP overexpression, alteration of tubulin isotypes, amino acid mutations in tubuhn, and microtubule dynamic changes are also involved in resistance to paclitaxel and other anti-microtubule agents. Here we concentrate on some recent results. Comprehensive descriptions can be found in reviews by Burkhart et a and Sangrajrang et al. ... 

Verdier-Pinard, R Wang, F. Martello, L. Burd, B. Orr, G. A. Horwitz, S. B. Analysis of tubulin isotypes and mutations from taxol-resistant cells by combined isoelectrofo-cusing and mass spectroscopy. Biochemistry, 2002, 42 5349-5357. 

Panda D, Miller HP, Baneijee A, Luduena RF, Wilson L. Microtubule dynamics in vitro are regulated by the tubulin isotype composition. Proc. Natl. Acad. Sci. U.S.A. 1994 91 11358-11362. 

Schwarz, P. M., Liggins, J. R. and Luduena, R. F. (1998) Beta-tubulin isotypes purified from bovine brain have different relative stabilities. Biochemistry, 37, 4687 1692. 

Derry, W. B., Wilson, L., Khan, I. A., el al. (1997) Taxol differentially modulates the dynamics of microtubules assembled from unfractionated and purified P-tubulin isotypes. Biochemistry, 36, 3554-3562. 

Haber, M., Burkhart, C. A., Regl, D. L., et al. (1995) Altered expression of Mbeta2, the class ii beta-tubulin isotype, in a murine J774.2 cell line with a high level of taxol resistance. Journal of Biological Chemistry, 270, 31269-31275. 

Huzil, J. T., Luduena, R. F. and Tuszynski, J. (2006) Comparative modelling of human P tubulin isotypes and implications for drug binding. Nanotechnology 17, S90-S100. 

Sharma RK, Netland PA. 2005. Class Illbeta-tubulin isotype expression in developing retina and identification of cell types expressing it. Invest Ophthalmol Vis Sci (ARVO abstract)... 

Two kinds of resistant biotypes have been noted one is highly-resistant (R) and is unaffected even by saturated solutions of dinitroaniline herbicide, whereas an intermediate-resistant (I) biotype is only 50X resistant to trifluralin and less than 10X resistant to oryzalin compared with the susceptible (S) biotype. Both R and I biotypes are cross-resistant to phosphoric amide herbicides. Tubulin from the R is able to polymerize into microtubules even in the presence of oryzalin, whereas that of the S biotypes cannot. Western blots of tubulin from the R biotype reveal two -tubulin isotypes whereas only one form is noted in the S biotype. Because the R biotype is hypersensitive to the microtubule-stabilizing agent taxol, it is likely that the R biotype is resistant by having hyperstabilized microtubules. The I biotype has no gross alteration in tubulin nor extreme sensitivity to taxol, indicating that this biotype has a different resistance mechanism than the R. 

Hoffman, P.N. and Cleveland, D.W. (1988) Neurofilament and tubulin expression recapitulates the developmental pattern during axonal regeneration induction of a specific 3-tubulin isotype. Proc. Natl. Acad. Sci. USA 85 4530-4533. 

Cytoskeletal components, e.g. tubulin isotypes, mitochondrial associated proteins Transcription factors Splicing regulators... 

The mitotic process depends on the structural and functional viability of microtubules (polymeric heterodimers consisting of isotypes of a- and (3- tubulin proteins). These distinct but nearly identical 50-kDa proteins lie adjacent to one another within the tubule and roll up to form an open, pipe-like cylinder akin to a hollow peppermint candy stick. A y-tubulin protein is found at the organizational center of the microtubule. The nature of the tubulin isotypes found in the microtubule are conserved throughout specific tissues within a given species and will impact the cell s sensitivity to mitosis inhibitors. 

Laing N, Dahilof B, Hartley-Asp B, et al. Interaction of estramustine with tubulin isotypes. Biochemistry 1997 36 871-878. 

Microtubules. Tubulin. Tubulin Isotypes, and Thyroid Hormone... 

Given the anatomical events that are occurring during this time and the ontogeny of these tubulin isotype iriRNAs, the cdteration of tubulin abundance may be of potential functional and anatomical... 

Fig. 6. PANEL A NORfflERN GEL HYBRIDIZATIC OF BGF inRNA IN TOTAL BRAIN and cerebral cortex from 1 and 7 day OID hvt/hvt and hvt/+ MICE. BGF iriRNA joas (Stressed in abundance in the 1 day hvt/hvt oerdDral cortex versus the 1 day hvt/-h cerdDral cortex. PANEL B NORIHERN GEL HYBRIDIZATICN of F 05 ISOTYPE iriRNA in 1 DAY hyt/1 AND hvt/+ CEREBRAL CC9RTEX, The abundance of the 55 IriRNA was significantly reduced in the hvt/hvt OC versus the hyt/+ normal OC at 1 day of age. The abundance of H05 iriRNA in hyt/hyt and hvt/-t- total brain was not significantly different. However, the abundance of H95 iriRNA was d ressed in the 1 day hvt/+ versus hvt/hvt brain remainder (data not cwn) the brain remainder represented all of the brain minus the cer ral cortex frtxn the same animal. Therefore at 1 day, 1 5 iriRNA is depressed in hvt/hvt cer rcd cortex but increased in hvt/hvt brain remainder versus hvt/+ remainder. No abundance changes were noted for the tubulin isotypes H04 or total tubulin iriE in OC.

Similar to BGF, the ontogeny of these iriRNAs in our studies and those of others demonstrated a hi ier abundance of some iriRNAs, i.e. tubulin isotypes (Figure 5) in the late fetal and early neonatal period and the subsequent rapid decline for these iriE NAs. The constitutive stocikpiling of tubulin iriRNA likely precedes neuronal process outgrowth and the decrease in these sequences may correspond with the onset of tubulin protein synthesis and terminal naircaial differentiation (43). 

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