UROP Proceedings 2010-11

G Proteins and their Regulators in Cancer BiologyAdvisor : WONG Yung Hou / LIFSStudent : CHAN Sin Man / BICH(UROP1000, Summer 2011)Fragile Histidine Triad gene (FHIT) is a tumor suppressor gene. It is located in the humanchromosome 3p14.2 and it encompasses the most active common fragile site FRA3B. It isbelieve that this gene is altered in cancer simply because of the fragility of this active site. Theprotein product of FHIT is a member of a family of protein that binds nucleotide andcatalyzes the corresponding hydrolysis. The residue His96 of FHIT is essential for ithydrolytic activity and it has been reported that the hydrolytic activity of FHIT is lost whenthe His96 is replaced by Asn. However, this enzymatically inactive mutant is still capable ofinducing caspase-dependent apoptosis in cancer cells. This finding suggests that theyhydrolytic function of FHIT is not necessary for its tumor-suppressive function, but thebinding of substrate AP 3 A is essential.10