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

Sardina, Francesca; Conte, Andrea; Paladino, Simona; Pierantoni, Giovanna Maria; Rinaldo, Cinzia

doi:10.1016/j.bbamcr.2023.119465

Cited by 5 publications

(2 citation statements)

References 81 publications

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“…HPK-1 regulates autophagy gene expression and across diverse species HIPK family members directly regulate TFs ( Sardina et al, 2023 ), therefore we sought to identify TFs essential for HPK-1 overexpression within GABAergic neurons to induce autophagy. pha-4 (FOXA), mxl-2 (MLX), hlh-30 (TFEB), daf-16 (FOXO), and hsf-1 are all required in specific contexts for the induction of autophagy and longevity ( Hansen et al, 2008 ; Kumsta et al, 2017 ; Lapierre et al, 2013 ; Lapierre et al, 2015 ; Nakamura et al, 2016 ; O’Rourke and Ruvkun, 2013 ).…”

Section: Resultsmentioning

confidence: 99%

Homeodomain-interacting protein kinase maintains neuronal homeostasis during normal Caenorhabditis elegans aging and systemically regulates longevity from serotonergic and GABAergic neurons

Lázaro-Peña

Cornwell

Díaz-Balzac

et al. 2023

eLife

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Aging and the age-associated decline of the proteome is determined in part through neuronal control of evolutionarily conserved transcriptional effectors, which safeguard homeostasis under fluctuating metabolic and stress conditions by regulating an expansive proteostatic network. We have discovered the Caenorhabditis elegans homeodomain-interacting protein kinase (HPK-1) acts as a key transcriptional effector to preserve neuronal integrity, function, and proteostasis during aging. Loss of hpk-1 results in drastic dysregulation in expression of neuronal genes, including genes associated with neuronal aging. During normal aging hpk-1 expression increases throughout the nervous system more broadly than any other kinase. Within the aging nervous system, hpk-1 induction overlaps with key longevity transcription factors, which suggests hpk-1 expression mitigates natural age-associated physiological decline. Consistently, pan-neuronal overexpression of hpk-1 extends longevity, preserves proteostasis both within and outside of the nervous system, and improves stress resistance. Neuronal HPK-1 improves proteostasis through kinase activity. HPK-1 functions cell non-autonomously within serotonergic and GABAergic neurons to improve proteostasis in distal tissues by specifically regulating distinct components of the proteostatic network. Increased serotonergic HPK-1 enhances the heat shock response and survival to acute stress. In contrast, GABAergic HPK-1 induces basal autophagy and extends longevity, which requires mxl-2 (MLX), hlh-30 (TFEB), and daf-16 (FOXO). Our work establishes hpk-1 as a key neuronal transcriptional regulator critical for preservation of neuronal function during aging. Further, these data provide novel insight as to how the nervous system partitions acute and chronic adaptive response pathways to delay aging by maintaining organismal homeostasis.

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Section: Resultsmentioning

confidence: 99%

Homeodomain-interacting protein kinase maintains neuronal homeostasis during normal Caenorhabditis elegans aging and systemically regulates longevity from serotonergic and GABAergic neurons

Lázaro-Peña

Cornwell

Díaz-Balzac

et al. 2023

eLife

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“…As a consequence of the interplay with multiple molecular pathways, HIPK2 regulates basic cellular functions, such as cell proliferation, apoptosis, DNA damage response, cytokinesis, protein stability, and transcription [18,[20][21][22][23]. These basic functions of HIPK2 may explain its key role in several biological processes, including development, fibrosis, angiogenesis, and neurodegeneration [24][25][26][27][28], as well as its function as a "bona fide" tumor suppressor [16].…”

Section: Hipk2 Function and Dysfunctionmentioning

confidence: 99%

The Sweet Side of HIPK2

Garufi

D’Orazi

Pistritto

et al. 2023

Cancers

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HIPK2 is an evolutionary conserved protein kinase which modulates many molecular pathways involved in cellular functions such as apoptosis, DNA damage response, protein stability, and protein transcription. HIPK2 plays a key role in the cancer cell response to cytotoxic drugs as its deregulation impairs drug-induced cancer cell death. HIPK2 has also been involved in regulating fibrosis, angiogenesis, and neurological diseases. Recently, hyperglycemia was found to positively and/or negatively regulate HIPK2 activity, affecting not only cancer cell response to chemotherapy but also the progression of some diabetes complications. The present review will discuss how HIPK2 may be influenced by the high glucose (HG) metabolic condition and the consequences of such regulation in medical conditions.

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Neuronal HIPK2-HDAC3 axis regulates mitochondrial fragmentation to participate in stroke injury and post-stroke anxiety like behavior

Yang,

Zhu,

Peng

et al. 2024

Experimental Neurology

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

Cited by 5 publications

References 81 publications

Homeodomain-interacting protein kinase maintains neuronal homeostasis during normal Caenorhabditis elegans aging and systemically regulates longevity from serotonergic and GABAergic neurons

Homeodomain-interacting protein kinase maintains neuronal homeostasis during normal Caenorhabditis elegans aging and systemically regulates longevity from serotonergic and GABAergic neurons

The Sweet Side of HIPK2

Neuronal HIPK2-HDAC3 axis regulates mitochondrial fragmentation to participate in stroke injury and post-stroke anxiety like behavior

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