Abstract
The c-Jun N-terminal kinase (JNK) is highly evolutionarily conserved and plays important roles in a broad range of physiological and pathological processes. The WD40-repeat protein 62 (WDR62) is a scaffold protein that recruits different components of the JNK signaling pathway to regulate several human diseases including neurological disorders, infertility, and tumorigenesis. Recent studies revealed that WDR62 regulates the process of neural stem cell mitosis and germ cell meiosis through JNK signaling. In this review we summarize the roles of WDR62 and JNK signaling in neuronal and non-neuronal contexts and discuss how JNK-dependent signaling regulates both processes. WDR62 is involved in various human disorders via JNK signaling regulation, and may represent a promising therapeutic strategy for the treatment of related diseases.
Highlights
The WD40 repeat (WDR) domain is among the most abundant protein–protein interaction domains involved in several biological pathways, and that are frequently implicated in disease mechanisms (Schapira et al, 2017)
The Jun N-terminal kinase (JNK) signaling pathway is considered as a novel and promising therapeutic target for various biological diseases, understanding its interaction with proteins and their mutual regulation is of great importance
Studies on HEK-293 cell line revealed the interaction between WD40-repeat protein 62 (WDR62) and JNKs in the absence of and after stimuli (Wasserman et al, 2010)
Summary
C-Jun N-terminal kinases (JNKs) form a major signaling cassettes of the mitogen-activated protein kinase (MAPK) pathway. In HCT116 cells, high glucose, insulin, and palmitic acid triggered the centrosome amplification and enhance the expressions of JNK1 and signal transducer and activator of transcription 3 (Stat3) (Lu et al, 2019) These results indicate the important role of JNKs especially JNK1 in the cellular stress response. During the fetal period (post-conceptual weeks (PCW) 15–21), WDR62 exhibited high expression levels in the ventricular zone (VZ) and subventricular zone (SVZ), compared to other cortical layers (Figure 1A) This is consistent with the important roles of WDR62 in neural progenitor cell (NPC) proliferation and differentiation. The spindle pole localization of WDR62 and mitotic progression are obviously defective in patient-derived fibroblasts, which become transiently arrested at the prometaphase (Sgourdou et al, 2017) These results reinforce importance of WDR62 in mitosis regulation. JNK signaling plays important roles in embryonic development, brain morphogenesis, and neuronal
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