Dual role for TGF-β1 in apoptosis

The exposure of cells to TGF-beta 1 can trigger a variety of cellular responses including the inhibition of cell growth, migration, differentiation and apoptosis. TGF-beta 1-regulated apoptosis is cell type and context-dependent, indeed TGF-beta 1 provides signals for both cell survival or apoptosis. The molecular mechanisms underlying the role of TGF-beta 1 in apoptosis remains unclear. The proteins that primarily mediate the intracellular signaling of TGF-beta 1 are the members of the Smad family. Nevertheless, TGF-beta 1 signaling can also cooperate with the death receptor apoptotic pathway (Fas, TNF), with the intracellular modulators of apoptosis JNK and p38 MAP kinases, Akt, NF-kappa B, and with the mitochondrial apoptotic pathway mediated by members of the Bcl-2 family. Moreover, the involvement of TGF-beta 1 in the production of oxidative stress and in preventing the inflammatory processes required for the clearance of apoptotic bodies is further evidence of its integration into apoptotic pathways. The interaction and balance between different stimuli provides the basis for the pro- or anti-apoptotic output of TGF-beta 1 signaling in a given cell. (c) 2004 Elsevier Ltd. All rights reserved.