Autophagy gets a brake: DAP1, a novel mTOR substrate, is activated to suppress the autophagic process.

Autophagy, a highly regulated catabolic process, is controlled by the action of positive and negative regulators. While many of the positive mediators of autophagy have been identified, very little is known about negative regulators that might counterbalance the process. We recently identified deathassociated protein 1 (DAP1) as a suppressor of autophagy and as a novel direct substrate of mammalian target of rapamycin (mTOR).

DAP1, a novel substrate of mTOR, negatively regulates autophagy.

Autophagy, a catabolic process responsible for the degradation of cytosolic components, is upregulated when nutrient supplies are limited. A critical step in autophagy induction comprises the inactivation of a key negative regulator of the process, the Ser/Thr kinase mammalian target of rapamycin (mTOR). Thus far, only a few substrates of mTOR that control autophagy have been identified, including ULK1 and Atg13, both of which function as positive mediators.

DAP5 promotes cap-independent translation of Bcl-2 and CDK1 to facilitate cell survival during mitosis.

DAP5 is an eIF4G protein previously implicated in mediating cap-independent translation in response to cellular stresses. Here we report that DAP5 is crucial for continuous cell survival in nonstressed cells. The knockdown of endogenous DAP5 induced M phase-specific caspase-dependent apoptosis.