Figure 1.

MAP3K1 domain organization and dual roles in cell survival and apoptosis. (A) Schematic structure of MAP3K1. It contains a SWIM and a RING zinc finger domain near the N-terminus and a serine/threonine kinase domain at the C-terminus. Caspase-3 cleavage occurs at the aspartate 874 of the mouse MAP3K1, which is equivalent to residue 878 of the human homolog. The protein domain structure was created using DOG 1.0 program.¹⁷ MAP3K1 also harbors binding sites for multiple upstream and downstream proteins indicated by the arrows. (B) MAP3K1 has a switch-like function that determines cell fate. Activation of MAP2K4/7-JNK-c-Jun, MAP2K1/2-ERK1/2, and NF-κB mediated by full length MAP3K1 promotes cell survival while caspase cleavage, which generates the soluble active kinase domain, induces apoptosis. MAP3K1 also ubiquitylates c-Jun and ERK1/2, leading to their degradation.