BMS 860 Lecture Notes - Lecture 3: Chronic Myelogenous Leukemia, Antigen, Philadelphia Chromosome
26 Feb 2017
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Research question: does bladder carcinoma dna carry cancer causing genes (oncogenes): transformation occurs at low frequency, only a small subset of genes are causing transformation. Small portion of these complexes enters the nucleus and integrates into the genome. Weinberg discovered mutant version of a proto-oncogene ras. Ggc (glycine) changed to gtc (valine) - proto-oncogene became oncogene. Ras is a gtp binding protein that normally cycles between an active gtp bound state and inactive gdp state. Inactive ras needs gef (guanine exchange factors) to catalyze the exchange of gtp. Gap catalyzes the hydrolysis back to gdp. Ras point mutation affects the gtp hydrolysis site inhibiting gtp hydrolysis. Ras protein gets stuck in its gtp bound state. Ras isoforms are frequently mutated in human cancers. Ras subfamily: family of related proteins expressed in all animal cell lineages and organs, small gtpase proteins involved in transmitting growth signals in cells. Ras subfamily: h-ras (harvey ras), k-ras (kristen ras), n-ras (neuroblastoma ras)
