Novel binding of the mitotic regulator TPX2 (target protein for Xenopus kinesin-like protein 2) to importin-alpha.

ABSTRACT: Several aspects of mitotic spindle assembly are orchestrated by the Ran GTPase through its modulation of the interaction between spindle assembly factors and importin-alpha. One such factor is TPX2 that promotes microtubule assembly in the vicinity of chromosomes. TPX2 is inhibited when bound to importin-alpha, which occurs when the latter is bound to importin-beta. The importin-alpha:beta interaction is disrupted by the high RanGTP concentration near the chromosomes, releasing TPX2. In more distal regions, where Ran is predominantly GDP-bound, TPX2 remains bound to importin-alpha and so is inhibited. Here we use a combination of structural and biochemical methods to define the basis for TPX2 binding to importin-alpha. A 2.2 A resolution crystal structure shows that the primary nuclear loc

SUBMITTER: Giesecke A 

PROVIDER: S-EPMC2878527 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature