TGF-β-dependent Cell Growth Arrest and Apoptosis

Abstract

Received 16 November 2001Transforming growth factor beta (TGF-β) is a member of alarge family of multifunctional secreted polypeptides that arepotent regulators of cell growth, differentiation, and matrixproduction (Massague, 1998; Dijke et al., 2000; Derynck etal., 2001).TGF-β was initially identified and named on the basis of itsability to stimulate fibroblast growth in soft agar, but it is nowthe best-studied growth inhibitory protein. Its molecularcomponents at each step in the TGF-β signaling pathway havebeen identified as tumor suppressors (Massague, 1998). Overthe last two decades, the TGF-β family has emerged as amajor source of signals that control cell growth anddifferentiation (Massague et al., 2000). Members of the TGF-β family produce different effects, depending on the type andstate of the cell. The signals of TGF-β family members aretransduced across the plasma membrane by the heteromericinteraction of two receptors, types I and II, which are serine/threonine kinases. The initiation of the signaling requiresbinding of TGF-β to the TGF-β type II receptor, aconstitutively active serine/threonine kinase, whichsubsequently transphosphorylates the TGF-β type I receptor.The activated type I receptor initiates intracellular signalingthrough the activation of specific Smad proteins. Smads relaysignals into the nucleus where they, together with otherproteins, direct transcriptional responses (Massague, 2000).In this review, we will focus on how TGF-β mediates cellgrowth arrest and apoptosis.