HIPK2 in the physiology of nervous system and its implications in neurological disorders

HIPK2 is an evolutionary conserved serine/threonine kinase with multifunctional roles in stress response, embryonic development and pathological conditions, such as cancer and fibrosis. The heterogeneity of its interactors and targets makes HIPK2 activity strongly dependent on the cellular context,...

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Published in:Biochimica et biophysica acta. Molecular cell research 2023-06, Vol.1870 (5), p.119465-119465, Article 119465
Main Authors: Sardina, F., Conte, A., Paladino, S., Pierantoni, G.M., Rinaldo, C.
Format: Article
Language:English
Subjects:
Animals
Carrier Proteins - metabolism
HIPK2
Humans
Kinase
Molecular medicine
Nervous System Diseases - genetics
Neurological disorders
Protein Serine-Threonine Kinases - genetics
Protein Serine-Threonine Kinases - metabolism
Signal Transduction
Signaling
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Summary:HIPK2 is an evolutionary conserved serine/threonine kinase with multifunctional roles in stress response, embryonic development and pathological conditions, such as cancer and fibrosis. The heterogeneity of its interactors and targets makes HIPK2 activity strongly dependent on the cellular context, and allows it to modulate multiple signaling pathways, ultimately regulating cell fate and proliferation. HIPK2 is highly expressed in the central and peripheral nervous systems, and its genetic ablation causes neurological defects in mice. Moreover, HIPK2 is involved in processes, such as endoplasmic reticulum stress response and protein aggregate accumulation, and pathways, including TGF-β and BMP signaling, that are crucial in the pathogenesis of neurological disorders. Here, we review the data about the role of HIPK2 in neuronal development, survival, and homeostasis, highlighting the implications in the pathogenesis of neurological disorders, and pointing out HIPK2 potentiality as therapeutic target and diagnostic or prognostic marker. •The kinase HIPK2 is highly expressed in the central and peripheral nervous system.•HIPK2 modulates several pathways in a cell- and environment-dependent manner.•HIPK2 plays a critical role in neuronal homeostasis and development.•HIPK2 is implicated in neurodegeneration by regulating protein turnover and cell death.•Altered HIPK2 functions are found in different neurological disorders.
ISSN:0167-4889
1879-2596
DOI:10.1016/j.bbamcr.2023.119465