MEKK3 coordinates with FBW7 to regulate WDR62 stability and neurogenesis

MEKK3 coordinates with FBW7 to regulate WDR62 stability and neurogenesis

how WDR62 is regulated and hence controls neurogenesis and brain size remains elusive.

the coordinated reciprocal and bidirectional regulation among MEKK3, FBW7, WDR62, and JNK1, is required for fine-tuned JNK signaling for the control of balanced NPC self-renewal and differentiation during cortical development.

Establishment of the mammalian neocortex requires precise control of proliferation and self-renewal of neural progenitor cells (NPCs), as well as the differentiation of NPCs and neuronal migration [1–4]. Defects in these processes lead to brain disorders

How MEKK3 and JNK1 stabilize WDR62 and activate JNK needs to be explored in the future.

 the scaffold protein WDR62 organizes a protein complex that includes MEKK3, MKKs, and JNK1 to control the proliferation and differentiation of NPCs during corticogenesis (Fig 8). The expression of WDR62 is fine-tuned both positively by MEKK3 and JNK activity and negatively by JNK-induced phosphorylation of WDR62 at T1053. Thus, the coordinated reciprocal and bidirectional regulation among WDR62, MEKK3, JNK1, and FBW7 fine-tunes JNK signaling to control the balance between proliferation and differentiation of NPCs and prevent superfluous cell death incurred by sustained JNK activation during brain development.