FIGURE 3.

The cross-links between ER stress/UPR and autophagy. PERK-mediated ATF4 translation induces CHOP. The transcriptional factors ATF4 and CHOP induce multiple ATG genes and autophagy regulatory factors alone or together. PERK also activates the MKK4/p38 pathway for CMA activation by phosphorylating LAMP2A. ATF6f activates the expression of GRP78, which inhibits AKT/mTORC1 activation, and DAPK1, which phosphorylates BECLIN1 to induce autophagy. IRE1α activation leads to JNK signaling, which induces BECLIN1 expression and also phosphorylates BCL2 to dissociate BECLIN1 for autophagy activation. XBP1s generation by IRE1α activation also transcriptionally activates BECLIN1 expression.