A cancer-associated aurora A mutant is mislocalized and misregulated due to loss of interaction with TPX2.

ABSTRACT: Mutations in protein kinases can drive cancer through alterations of the kinase activity or by uncoupling kinase activity from regulation. Changes to protein expression in Aurora A, a mitotic Ser/Thr kinase, are associated with the development of several human cancers, but the effects of somatic cancer-associated mutations have not been determined. In this study we show that Aurora A kinase activity is altered in different ways in three somatic cancer-associated mutations located within the catalytic domain; Aurora A(V174M) shows constitutively increased kinase activity, Aurora A(S155R) activity is decreased primarily due to misregulation, and Aurora A(S361*) activity is ablated due to loss of structural integrity. These alterations suggest vastly different mechanisms for the role of these

SUBMITTER: Bibby RA 

PROVIDER: S-EPMC2785160 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature