-GlcNAcylation: An Emerging Protein Modification Regulating the Hippo Pathway.

Cancers (Basel)

Glycosylation Network Research Center, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.

Published: June 2022

The balance between cellular proliferation and apoptosis and the regulation of cell differentiation must be established to maintain tissue homeostasis. These cellular responses involve the kinase cascade-mediated Hippo pathway as a crucial regulator. Hence, Hippo pathway dysregulation is implicated in diverse diseases, including cancer. -GlcNAcylation is a non-canonical glycosylation that affects multiple signaling pathways through its interplay with phosphorylation in the nucleus and cytoplasm. An abnormal increase in the -GlcNAcylation levels in various cancer cells is a potent factor in Hippo pathway dysregulation. Intriguingly, Hippo pathway dysregulation also disrupts -GlcNAc homeostasis, leading to a persistent elevation of -GlcNAcylation levels, which is potentially pathogenic in several diseases. Therefore, -GlcNAcylation is gaining attention as a protein modification that regulates the Hippo pathway. This review presents a framework on how -GlcNAcylation regulates the Hippo pathway and forms a self-perpetuating cycle with it. The pathological significance of this self-perpetuating cycle and clinical strategies for targeting -GlcNAcylation that causes Hippo pathway dysregulation are also discussed.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221189PMC
http://dx.doi.org/10.3390/cancers14123013DOI Listing

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