TGF-BETA SIGNALING AND CANCER - STRUCTURAL AND FUNCTIONAL CONSEQUENCES OF MUTATIONS IN SMADS

Transforming growth factor-beta (TGF-beta) and related cytokines contr ol the development and homeostasis of many tissues by regulating the e xpression of genes that determine cell phenotype, Recent progress has elucidated the way in which members of the TGF-beta family initiate th eir signal through transmembrane receptors and transmit it to target g enes via the Smad family of signal-transducing proteins. This review d escribes TGF-beta signaling pathways as currently understood and mutat ions of the genes that encode Smads that disrupt the function of these proteins and cause various forms of cancer.