ArticleThe Journal of biological chemistry2013
Reversible acetylation regulates salt-inducible kinase (SIK2) and its function in autophagy.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 55 citations in OpenAlex.
- Inhibition of SIK2 and SIK3 induces adaptive ER-phagy and creates a therapeutic vulnerability in ovarian cancer.Research square · 2026Article
- Acetylation modification in malignant progression and therapeutic resistance of gliomas.Frontiers in cell and developmental biology · 2026Review
- Inhibition of Salt-Inducible Kinase 2 Protects Motor Neurons From Degeneration in ALS by Activating Autophagic Flux and Enhancing mTORC1 Activity.CNS neuroscience & therapeutics · 2025Article
- SIK2 activates the autophagy‒apoptosis pathway through SP1 regulation to inhibit the progression of hepatocellular carcinoma.Frontiers in pharmacology · 2025Article
- Article
- Understanding the roles of salt-inducible kinases in cardiometabolic disease.Frontiers in physiology · 2024Review
- Distinct mouse models of Stargardt disease display differences in pharmacological targeting of ceramides and inflammatory responses.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The multiple roles of salt-inducible kinases in regulating physiology.Physiological reviews · 2023Review
- Polyamines and Physical Activity in Musculoskeletal Diseases: A Potential Therapeutic Challenge.International journal of molecular sciences · 2023Review
- Lysine Deacetylase Substrate Selectivity: Distinct Interaction Surfaces Drive Positive and Negative Selection for Residues Following Acetyllysine.Biochemistry · 2023Article
- Identification of a reciprocal negative feedback loop between tau-modifying proteins MARK2 kinase and CBP acetyltransferase.The Journal of biological chemistry · 2022Article
- Pannexin 1 channels facilitate communication between T cells to restrict the severity of airway inflammation.Immunity · 2021Article
- Salt-inducible kinase 2 regulates energy metabolism in rats with cerebral ischemia-reperfusion.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Article
- ZNRF1 Mediates Epidermal Growth Factor Receptor Ubiquitination to Control Receptor Lysosomal Trafficking and Degradation.Frontiers in cell and developmental biology · 2021Article
- SIK2 represses AKT/GSK3β/β-catenin signaling and suppresses gastric cancer by inhibiting autophagic degradation of protein phosphatases.Molecular oncology · 2021Article
- Critical review of non-histone human substrates of metal-dependent lysine deacetylases.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Review
- The potent roles of salt-inducible kinases (SIKs) in metabolic homeostasis and tumorigenesis.Signal transduction and targeted therapy · 2020Review
- Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy.Molecular neurodegeneration · 2020Article
- Salt inducible kinases as novel Notch interactors in the developing Drosophila retina.PloS one · 2020Article
- p53 at the Crossroads between Different Types of HDAC Inhibitor-Mediated Cancer Cell Death.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Salt-inducible kinase 2 (SIK2) is a serine/threonine protein kinase belonging to the AMP-activated protein kinase (AMPK) family. SIK2 has been shown to function in the insulin-signaling pathway during adipocyte differentiation and to modulate CREB-mediated gene expression in response to hormones and nutrients. However, molecular mechanisms underlying the regulation of SIK2 kinase activity remains largely elusive. Here we report a dynamic, post-translational regulation of its kinase activity that is coordinated by an acetylation-deacetylation switch, p300/CBP-mediated Lys-53 acetylation inhibits SIK2 kinase activity, whereas HDAC6-mediated deacetylation restores the activity. Interestingly, overexpression of acetylation-mimetic mutant of SIK2 (SIK2-K53Q), but not the nonacetylatable K53R variant, resulted in accumulation of autophagosomes. Further consistent with a role in autophagy, knockdown of SIK2 abrogated autophagosome and lysosome fusion. Consequently, SIK2 and its kinase activity are indispensable for the removal of TDP-43Δ inclusion bodies. Our findings uncover SIK2 as a critical determinant in autophagy progression and further suggest a mechanism in which the interplay among kinase and deacetylase activities contributes to cellular protein pool homeostasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.