Transforming mutations of RAC guanosine triphosphatases in human cancers
作者： M. Kawazu , T. Ueno , K. Kontani , Y. Ogita , M. Ando
关键词:
摘要: Members of the RAS superfamily small guanosine triphosphatases (GTPases) transition between GDP-bound, inactive and GTP-bound, active states thereby function as binary switches in regulation various cellular activities. Whereas HRAS, NRAS, KRAS frequently acquire transforming missense mutations human cancer, little is known oncogenic roles other GTPases, including Ras-related C3 botulinum toxin substrate (RAC) proteins. We show that sarcoma cell line HT1080 harbors both NRAS(Q61K) RAC1(N92I) mutant these mutants were able to transform fibroblasts, knockdown experiments indicated may be essential growth driver for this line. Screening RAC1, RAC2, or RAC3 lines public databases identified several RAC1 with some proteins, RAC1(P29S), RAC1(C157Y), RAC2(P29L), RAC2(P29Q), being found activated transforming. P29S, N92I, C157Y shown exist preferentially GTP-bound state a result rapid from GDP-bound state, rather than reduced intrinsic GTPase activity. Activating RAC GTPases thus wide variety cancers at low frequency; however, given their marked ability, proteins are potential targets development new therapeutic agents.
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