Fig. 1.

A schematic overview on how PML-RARα causes ER stress in AML is provided. Here, under physiological conditions, RARα can dissociate from coreceptors such as N-CoR. In PML-RARα⁺ AML, the binding is significantly increased. This leads to a conformational change of the N-CoR protein. The misfolded N-CoR protein is degraded by ERAD through activation of ATF6α. Through the lack of soluble and functional N-CoR, protein myeloid differentiation is prevented and activity of the tumor suppressor MAD is reduced