Fig. 3.

NMD promotes timely termination of the UPR. a The UPR can be thought of as a clock. If the stress is resolved in a timely manner, the result is homeostasis. Alternatively, prolonged stress leads to apoptosis. NMD promotes both maintenance of homeostasis and timely termination of the UPR. b NMD is suppressed by the UPR to allow for maximal activation of the UPR pathway. After the resolution of the stress, the UPR is downregulated, which is thought to rescue normal levels of NMD, thereby leading to further downregulation of the UPR. This regulatory spiral eventually leads to complete shut-off of the UPR pathway. c In chronic stress, the UPR is constitutively activated and NMD is suppressed, which, together, typically leads to apoptosis