Detection of human betaV-tubulin expression in epithelial cancer cell lines by tubulin proteomics.
Biochemistry
; 44(48): 15858-70, 2005 Dec 06.
Article
em En
| MEDLINE
| ID: mdl-16313188
ABSTRACT
Tubulin, the constitutive protein of microtubules, is a heterodimeric protein with an alpha and beta subunit, encoded in vertebrates by six and seven different genes, respectively. Each tubulin isotype can be identified by its divergent C-terminal sequence. Nevertheless, two groups of beta-tubulin isotypes can be distinguished by sequence alignment; one includes betaI-, betaII-, betaIVa-, and betaIVb-tubulin, and the other includes betaIII-, betaV-, and betaVI-tubulin. betaIII-tubulin overexpression has been associated with microtubule destabilization and resistance to Taxol. Recent data indicate that mouse betaV-tubulin overexpression in CHO cells results in profound microtubule disorganization and dependence of cells on Taxol for growth. Mouse and human betaV-tubulin sequences display several differences, such as their respective extreme C-terminus, suggesting that they may have different effects on microtubule stability and different affinities for drugs. When high-resolution isoelectric focusing, in-gel CNBr cleavage, and mass spectrometry were combined, we detected for the first time the betaV-tubulin protein in human cell lines and found that it was highly expressed in Hey, an epithelial ovarian cancer cell line. Our data confirm that human and rodent betaV-tubulins are distinct and indicate that, regardless of species, betaIII- and betaV-tubulin may be expressed in a complementary pattern at the protein level. Therefore, both betaIII- and betaV-tubulin expression levels should be systematically determined to assess the role of differential tubulin isotype expression in the response of tumors to drugs targeting microtubules.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tubulina (Proteína)
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article