β-微管蛋白结合蛋白Rbl2p对游离β-微管蛋白的保护作用。
Protection from free beta-tubulin by the beta-tubulin binding protein Rbl2p.
作者信息
Abruzzi Katharine C, Smith Adelle, Chen William, Solomon Frank
机构信息
Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
出版信息
Mol Cell Biol. 2002 Jan;22(1):138-47. doi: 10.1128/MCB.22.1.138-147.2002.
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.
未与α-微管蛋白形成异二聚体的游离β-微管蛋白可能具有毒性，会破坏微管的组装和功能。我们对细胞保护自身免受游离β-微管蛋白影响的机制感兴趣。本研究特别关注Rbl2p的功能，它与α-微管蛋白一样，能够拯救细胞免受游离β-微管蛋白的影响。对Rbl2p的哺乳动物同源物辅因子A的体外研究表明，Rbl2p/辅因子A可能参与微管蛋白折叠。我们在此表明，在相对于α-微管蛋白含有适度过量β-微管蛋白的细胞中，Rbl2p变得至关重要。然而，Rbl2p/辅因子A的这种关键活性并不依赖于体外测定所描述的反应。拯救β-微管蛋白毒性需要Rbl2p与β-微管蛋白的比例最小但低于化学计量。数据表明，Rbl2p与游离β-微管蛋白短暂结合，然后β-微管蛋白转变为无毒的聚集形式。
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