title: Protection from free beta-tubulin by the beta-tubulin binding protein Rbl2p.
abstract: Free beta-tubulin not in heterodimers with alpha-tubulin can be toxic, disrupting microtubule assembly and function. We are interested in the mechanisms by which cells protect themselves from free beta-tubulin. This study focused specifically on the function of Rbl2p, which, like alpha-tubulin, can rescue cells from free beta-tubulin. In vitro studies of the mammalian homolog of Rbl2p, cofactor A, have suggested that Rbl2p/cofactor A may be involved in tubulin folding. Here we show that Rbl2p becomes essential in cells containing a modest excess of beta-tubulin relative to alpha-tubulin. However, this essential activity of Rbl2p/cofactorA does not depend upon the reactions described by the in vitro assay. Rescue of beta-tubulin toxicity requires a minimal but substoichiometric ratio of Rbl2p to beta-tubulin. The data suggest that Rbl2p binds transiently to free beta-tubulin, which then passes into an aggregated form that is not toxic.
authors.affiliation: Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Katharine C
authors.initials: KC
authors.lastname: Abruzzi
authors.forename: Adelle
authors.initials: A
authors.lastname: Smith
authors.forename: William
authors.initials: W
authors.lastname: Chen
authors.forename: Frank
authors.initials: F
authors.lastname: Solomon
mesh_terms: D002850:Chromatography, Gel; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
chemical_list: C107852:CIN1 protein, S cerevisiae; D008869:Microtubule-Associated Proteins; C443671:RBL2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014404:Tubulin