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In the second part of Dr. Wittinghofer's talk he explains the link between GTPases and disease. Ras is both a key molecule in regulating normal cell growth and an oncogene in unregulated cancer cell growth. Mutations in Ras that prevent the hydrolysis of GTP to GDP lock Ras into an active state rendering it independent of upstream growth factor signals. Biophysical studies from Wittinghofer's lab solved the multiple steps in the hydrolysis of GTP to GDP and explained why particular mutations in either Ras or Ras-GAPs cause unregulated activation of Ras and tumor formation. Examples of other G-proteins that are unable to hydrolyse GTP and result in different diseases such as Retinitis Pigmentosa, are also presented.
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