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Fig. 3. (A) Smads in apoptosis. TGF-ß receptors induce through Smads the expression of DAPK, SHIP and TIEG pro-apoptotic genes. Smads also bind and inactivate the survival kinase Akt, thus promoting apoptosis. TGF-ß can also mobilize the mitochondrial serpin ARTS to the nucleus, which blocks XIAPs, the inhibitors of caspases, thus leading to apoptotic events. (B) The TAK1 pathway leading to apoptosis. The TGF-ß type I receptor binds Smad7, the type II receptor binds the pro-apoptotic protein Daxx, whereas BMP receptors bind XIAP and its interacting partners, TAB and TAK1. Both TGF-ß and BMP receptors activate TAK1, leading to MKK3, MKK4 or MKK7 activation. This activates JNK or p38, both of which lead to apoptosis of various cell types. In the Daxx pathway, HIPK2 phosphorylates Daxx (curved arrow), which then activates MKK4 and MKK7.

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