The roles of Cys124 and Ser239 in the functional properties of human βIII tubulin

Patrick A. Joe, Asok Banerjee, Richard F. Ludueña

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Tubulin is the target for some very powerful anti-mitotic and anti-tumor drugs. The βIII tubulin isotype is found in very few normal tissues, but is often found in tumors, where it has been implicated in resistance to anti-tumor drugs. The βIII isotype occurs in fish, amphibians, birds and mammals and its unique features are highly conserved in evolution. One of these features is the replacement of cys239 by ser239. Cys239 is unusual in being highly sensitive to oxidation; in fact, oxidation of this residue inhibits microtubule assembly. The βIII isotype also has a very unusual cys124, where other β isotypes have ser/ala124. The striking conservation in βIII of vertebrates strongly suggests that cys124 and ser239 play functional roles. We have prepared the C124S and S239C mutants of βIII and tested their effects on the functional properties of tubulin. We have found that both the βIII C124S and βIII S239C mutants bind colchicine less well than does wild-type αβIII, and also make transfected HeLa cells more resistant to colchicine. However, the double mutant, βIII C124S/S239C, binds colchicine still less well than do either of the single mutants, but in contrast to the former, the double mutant increases the cells' sensitivity to colchicine. Our results indicate that the roles that these residues play in colchicine binding and microtubule integrity are far more complex than previously imagined and that the specific residues at which βIII differs from the other isotypes act collectively to keep βIII in a functional conformation.

Original languageEnglish (US)
Pages (from-to)476-486
Number of pages11
JournalCell Motility and the Cytoskeleton
Volume65
Issue number6
DOIs
StatePublished - Jun 2008

Keywords

  • Class III β-tubulin
  • Colchicine
  • Cysteine
  • Microtubules
  • Tubulin
  • βIII-tubulin

ASJC Scopus subject areas

  • Structural Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The roles of Cys124 and Ser239 in the functional properties of human βIII tubulin'. Together they form a unique fingerprint.

  • Cite this