Telomerase RNA Mutated in Autosomal Dyskeratosis Congenita Reconstitutes a Weakly Active Telomerase Enzyme Defective in Telomere Elongation

Abstract

The PI3K signaling pathway is upregulated in numerous cancers. The catalytic subunit p110alpha of PI3K shows hot spot mutations in nearly 30% of several types of solid tumors. The most prominent of these mutations result in gain of enzymatic function, activate Akt signaling and induce oncogenic cellular transformation. The mutated p110alpha proteins are ideal targets for specific small molecule inhibitors that discriminate between the oncogenic and the wild-type forms of the enzyme. Such inhibitors could become highly effective anti-cancer drugs.