ArticleCell death and differentiation2023
Lysine methylation of PPP1CA by the methyltransferase SUV39H2 disrupts TFEB-dependent autophagy and promotes intervertebral disc degeneration.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Davunetide promotes structural and functional recovery of the injured spinal cord by promoting autophagy.Neural regeneration research · 2026Article
- Itgb1-Mediated Stabilization of Vimentin Alleviates Excessive Mechanical Stress-Induced Nucleus Pulposus Cell Pyroptosis and Intervertebral Disc Degeneration via PINK1-Parkin-Dependent Mitophagy.Cell proliferation · 2026Article
- A continuous DNA repairing system for alleviating intervertebral disc degeneration.Journal of nanobiotechnology · 2026Article
- Epigenetic H3K4me3 activation of miR-155-5p promotes intervertebral disc degeneration via autophagy and ageing in nucleus pulposus cells.Non-coding RNA research · 2026Article
- Epigenetic crossroads in intervertebral disc degeneration: Unlocking novel therapeutic avenues (Review).Molecular medicine reports · 2026Review
- Exploring the Interconnections Between Mitochondrial Dysfunction and Polycystic Ovary Syndrome: A Comprehensive Integrated Analysis.Biochemical genetics · 2026Article
- Metabolic reprogramming in intervertebral disc degeneration: mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- The Role of TFEB-Regulated Autophagy in Intervertebral Disc Degeneration and Its Therapeutic Potential.Journal of inflammation research · 2026Review
- The multifaceted role of SQSTM1/p62 in disc degeneration: A master regulator of cellular stress responses.Biochemistry and biophysics reports · 2025Review
- Targeting the ROS-ferroptosis-inflammation cycle with a nanozyme-functionalized hydrogel for intervertebral disc repair.Nature communications · 2025Article
- Taurine can restrict MtdsRNA mediated pyroptosis by enhancing mitophagy in nucleus pulposus cells.Cell communication and signaling : CCS · 2025Article
- TGFBI Inhibits the Pyroptosis of Macrophages to Ameliorate Septic Shock.Journal of cellular and molecular medicine · 2025Article
- Machine learning-enabled identification of nucleus pulposus senescence-associated genes as potential biomarkers for intervertebral disc degeneration.European journal of medical research · 2025Article
- DDX1 methylation mediated MATR3 splicing regulates intervertebral disc degeneration by initiating chromatin reprogramming.Nature communications · 2025Article
- Exosomes derived from MSCs exposed to hypoxic and inflammatory environments slow intervertebral disc degeneration by alleviating the senescence of nucleus pulposus cells through epigenetic modifications.Bioactive materials · 2025Article
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- KMT2A regulates the autophagy-GATA4 axis through METTL3-mediated mBone research · 2024Article
- Magnetically attracting hydrogel reshapes iron metabolism for tissue repair.Science advances · 2024Article
- S100A4 targets PPP1CA/IL-17 to inhibit the senescence of sheep endometrial epithelial cells.Frontiers in veterinary science · 2024Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Impaired transcription factor EB (TFEB) function and deficient autophagy activity have been shown to aggravate intervertebral disc (IVD) degeneration (IDD), yet the underlying mechanisms remain less clear. Protein posttranslational modifications (PTMs) are critical for determining TFEB trafficking and transcriptional activity. Here, we demonstrate that TFEB activity is controlled by protein methylation in degenerated nucleus pulposus cells (NPCs), even though TFEB itself is incapable of undergoing methylation. Specifically, protein phosphatase 1 catalytic subunit alpha (PPP1CA), newly identified to dephosphorylate TFEB, contains a K141 mono-methylated site. In degenerated NPCs, increased K141-methylation of PPP1CA disrupts its interaction with TEFB and subsequently blocks TEFB dephosphorylation and nuclear translocation, which eventually leads to autophagy deficiency and NPC senescence. In addition, we found that the PPP1CA-mediated targeting of TFEB is facilitated by the protein phosphatase 1 regulatory subunit 9B (PPP1R9B), which binds with PPP1CA and is also manipulated by K141 methylation. Further proteomic analysis revealed that the protein lysine methyltransferase suppressor of variegation 3-9 homologue 2 (SUV39H2) is responsible for the K141 mono-methylation of PPP1CA. Targeting SUV39H2 effectively mitigates NPC senescence and IDD progression, providing a potential therapeutic strategy for IDD intervention.
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