SUMMARY PARAGRAPH for RBL2
Microtubules are conserved cytoskeletal elements that form by the polymerization of alpha- and beta-tubulin heterodimers. The formation of polymerization-competent tubulin heterodimers requires that alpha-tubulin and beta-tubulin be properly folded. Specific cofactors are required for the folding of alpha- and beta-tubulin in vitro and homologs of these cofactors have been found in many organisms, including S.cerevisiae (reviewed in 5).
In S.cerevisiae, RBL2 is a non-essential gene that encodes the yeast structural and functional homolog of mouse beta-tubulin cofactor A 1. Cofactor A can complement Rbl2p function in vivo 1. Cofactor A is required in the post-chaperonin tubulin folding pathway in vitro, specifically for the folding of beta-tubulin 6. RBL2 was isolated in a genetic screen for genes that when overexpressed rescue the lethality caused by excess beta-tubulin (encoded by the TUB2 gene) 1. A high ratio of beta-tubulin to alpha-tubulin is lethal in S.cerevisiae, causing microtubule disassembly. RBL2 overexpression rescues beta-tubulin-associated lethality as efficiently as alpha-tubulin, and Rbl2p binds to beta-tubulin in vivo in a complex that excludes alpha-tubulin 1.
rbl2 null mutants are viable but supersensitive to benomyl, a microtubule depolymerizing drug 1. rbl2 null mutants are synthetically lethal in combination with specific alpha-tubulin mutants, most notably tub1-724, which creates an unstable heterodimer with beta-tubulin 1, 7, 8. In addition to acting in the beta-tubulin formation pathway, Rbl2p may also serve a protective function by sequestering free beta-tubulin monomers 1, 7, 8. However, excess RBL2 is lethal when the tubulin heterodimer is unstable, as overexpression of RBL2 in tub1-724, pac2/cofactorE, or cin1/cofactor D mutants causes lethality by depolymerization of microtubules 7.
Last updated: 2003-12-30