Editors' ChoiceCancer Biology

RasGAP in the Balance

STKE  02 Jul 2002:
Vol. 2002, Issue 139, pp. tw238-TW238
DOI: 10.1126/stke.2002.139.tw238

Ras GTPase-activating proteins (RasGAPs) are best known as negative regulators because they stimulate the hydrolysis of GTP by Ras. However, in cancer cells that express an oncogenic form of Ras, RasGAP can no longer deactivate Ras. Instead, it acts as a Ras effector, promoting cell proliferation. Gigoux et al. report that an interaction between the Src homology 3 (SH3) domain of RasGAP and the kinase domain of the serine-threonine kinase Aurora may account for this effect. The interaction may directly or indirectly regulate Aurora activity, which is required for mitosis. The antiapoptotic protein Survivin was also detected in a complex with Aurora and RasGAP. The authors propose that the ternary complex may regulate both cell division and apoptosis in tumor cells.

V. Gigoux, S. L'Hoste, F. Raynaud, J. Camonis, C. Garbay, Identification of Aurora kinases as RasGAP Src homology 3 domain-binding proteins. J Biol. Chem. 277, 23742-23746 (2002). [Abstract] [Full Text]