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Preface/Front Matter

R. Derynck, K. Miyazono


It has been close to 30 years since the discovery of transforming growth factors as secreted proteins with the ability to induce a reversible transformed phenotype under some cell culture conditions. Not surprisingly, these findings were very skeptically received, because around that time, oncogenes were being discovered as genes encoding cell-autonomous proteins that genetically endowed the cells to behave and function as cancer cells. The discovery of transforming growth factors led to the concept of autocrine control of cell transformation and, later, of cell differentiation and function. Following its discovery, transforming growth factor-β (TGF-β) was shown to have key functions in a variety of cell and tissue contexts, most notably in cell proliferation and differentiation, development, malignant transformation, and cancer progression. In fact, TGF-β was rediscovered several times as secreted proteins with diverse activities, for example, cartilage-inducing factor, glioblastoma-derived T-cell suppressor factor (GTsF), and growth inhibitor from BSC-1 cells.

Following the elucidation of the polypeptide sequence of TGF-β1, it became rapidly apparent through cDNA cloning that there is a family of structurally related proteins that together form the TGF-β family that functions in all metazoans from Planaria and nematodes to Drosophila and vertebrates. Activins and inhibins were discovered as hormones that act on pituitary gonadotrope cells and regulate the release of follicle-stimulating hormone. Research on bone morphogenetic proteins (BMPs) was launched by the observation that the demineralized bone matrix contains bioactive proteins capable of inducing bone and cartilage formation in muscular tissues. Purification of these proteins and subsequent cDNA cloning

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