ArticleCell death and differentiation2016
Phosphorylation of CHIP at Ser20 by Cdk5 promotes tAIF-mediated neuronal death.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- CDK5-triggered G6PD phosphorylation at threonine 91 facilitating redox homeostasis reveals a vulnerability in breast cancer.Acta pharmaceutica Sinica. B · 2025Article
- 5-HTJournal of advanced research · 2025Article
- Targeting chaperone modifications: Innovative approaches to cancer treatment.The Journal of biological chemistry · 2024Review
- Induced degradation of lineage-specific oncoproteins drives the therapeutic vulnerability of small cell lung cancer to PARP inhibitors.Science advances · 2024Article
- PARP1 inhibitors induce pyroptosis via caspase 3-mediated gasdermin E cleavage.Biochemical and biophysical research communications · 2023Article
- Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity.Sub-cellular biochemistry · 2023Article
- Chaperone-assisted E3 ligase CHIP: A double agent in cancer.Genes & diseases · 2022Review
- RING-finger protein 166 plays a novel pro-apoptotic role in neurotoxin-induced neurodegeneration via ubiquitination of XIAP.Cell death & disease · 2020Article
- CHIP phosphorylation by protein kinase G enhances protein quality control and attenuates cardiac ischemic injury.Nature communications · 2020Article
- PARP1 inhibitors trigger innate immunity via PARP1 trapping-induced DNA damage response.eLife · 2020Article
- Site-specific phosphorylation of Fbxw7 by Cdk5/p25 and its resulting decreased stability are linked to glutamate-induced excitotoxicity.Cell death & disease · 2019Article
- CDK5 Regulates PD-L1 Expression and Cell Maturation in Dendritic Cells of CRSwNP.Inflammation · 2019Article
- Computational Simulations Identified Two Candidate Inhibitors of Cdk5/p25 to Abrogate Tau-associated Neurological Disorders.Computational and structural biotechnology journal · 2019Article
- The acetylation of cyclin-dependent kinase 5 at lysine 33 regulates kinase activity and neurite length in hippocampal neurons.Scientific reports · 2018Article
- K6 linked polyubiquitylation of FADD by CHIP prevents death inducing signaling complex formation suppressing cell death.Oncogene · 2018Article
- Covalent ISG15 conjugation to CHIP promotes its ubiquitin E3 ligase activity and inhibits lung cancer cell growth in response to type I interferon.Cell death & disease · 2018Article
- Notch and Cdk5 in Zebrafish Mindbomb Mutant: Co-regulation or Coincidence?Folia biologica · 2018Review
- Aurora Kinase A Promotes AR Degradation via the E3 Ligase CHIP.Molecular cancer research : MCR · 2017Article
- Cdk5 links with DNA damage response and cancer.Molecular cancer · 2017Review
- Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase and its dysregulation is implicated in neurodegenerative diseases. Likewise, C-terminus of Hsc70-interacting protein (CHIP) is linked to neurological disorders, serving as an E3 ubiquitin ligase for targeting damaged or toxic proteins for proteasomal degradation. Here, we demonstrate that CHIP is a novel substrate for Cdk5. Cdk5 phosphorylates CHIP at Ser20 via direct binding to a highly charged domain of CHIP. Co-immunoprecipitation and ubiquitination assays reveal that Cdk5-mediated phosphorylation disrupts the interaction between CHIP and truncated apoptosis-inducing factor (tAIF) without affecting CHIP's E3 ligase activity, resulting in the inhibition of CHIP-mediated degradation of tAIF. Lentiviral transduction assay shows that knockdown of Cdk5 or overexpression of CHIP(S20A), but not CHIP(WT), attenuates tAIF-mediated neuronal cell death induced by hydrogen peroxide. Thus, we conclude that Cdk5-mediated phosphorylation of CHIP negatively regulates its neuroprotective function, thereby contributing to neuronal cell death progression following neurotoxic stimuli.
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