FIG. 9.

Schematic representation of signaling pathway that mediates Gadd45a-induced apoptosis. In cellular response to genotoxic stress and growth arrest signals, Gadd45a is highly induced. Increased Gadd45a protein interacts with EF-1α, a microtubule-severing protein that maintains cytoskeletal stability, and disrupts the stability of the cytoskeleton. Bim protein is in turn released from destabilized microtubule-associated protein complexes and translocates to mitochondria. Induction of Bim in mitochondria relieves Bax from Bcl-2-bound complexes and induces release of cytochrome c. Finally, cells undergo apoptosis.