Ornithine aminotransferase (OAT): a target for anticancer drugs
AssigneeBoard of Regents, The University of Texas System
InventorsPatrick Harran, Xiaodong Wang, Gelin Wang
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Abstract
Ornithine δ-aminotransferase (OAT) facilitates microtubule assembly in addition to its aminotransferase activity in mitochondria. An N-terminal proteolysis of the first 17 amino acids of OAT block its transport to the mitochondria. The resultant truncated protein (OATC) forms specific complexes with mitotic spindle promoting proteins such as Eg5 and takes on a Ran-dependent spindle-assembly activity. Methods and compositions for inhibiting mitotic spindle assembly in a cell by specifically inhibiting OAT, and methods for screening for inhibitors of (1) the spindle-assembly function of OAT, (2) the protease that N-truncates OAT, (3) the OAT/RanGTP association and (4) the OAT/Eg5 association are disclosed.
Claims6
A method to identify an inhibitor of ornithine δ-aminotransferase (OAT)-facilitated spindle formation comprising the steps of:
- determining that a candidate agent binds an OAT that promotes spindle assembly;
- and
- contacting a spindle assembly system wherein spindle assembly is facilitated by the OAT, with the agent under conditions wherein the agent binds the OAT and thereby inhibits the spindle assembly resulting in a defective spindle assembly as compared with a control spindle assembly, and thereby identifies the agent as an inhibitor of OAT-facilitated spindle formation, wherein the OAT is wild-type N-truncated mammalian OAT beginning with Val18.
Dependencies are inferred from the claim text.