ArticleThe Journal of biological chemistry2008
Phosphorylation of murine caspase-9 by the protein kinase casein kinase 2 regulates its cleavage by caspase-8.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 57 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- The Prominent Role of Serines 302/307 in the Activity and Stability of Human Caspase9: Appraisal of the S302D and S307D Variants.Biochemical genetics · 2026Article
- The role of vitamin C in melanoma cell death via activation of cytochrome C and TNF-α protein expression.Scientific reports · 2025Article
- Diazinon-induced Cognitive Impairment: Alternations in Amyloid Precursor Proteins, and TNF-α Expression in the Hippocampus of Adult Rats.Current topics in medicinal chemistry · 2025Article
- PI3K-AKT-mediated phosphorylation of Thr260 in CgCaspase-3/6/7 regulates heat-induced activation in oysters.Communications biology · 2024Article
- Inhibition of Caspase 3 and Caspase 9 Mediated Apoptosis: A Multimodal Therapeutic Target in Traumatic Brain Injury.Current neuropharmacology · 2023Review
- Evaluation of the effects of phosphorylation of synthetic peptide substrates on their cleavage by caspase-3 and -7.The Biochemical journal · 2021Article
- Caspase-9: A Multimodal Therapeutic Target With Diverse Cellular Expression in Human Disease.Frontiers in pharmacology · 2021Review
- Melatonin/Nrf2/NLRP3 Connection in Mouse Heart Mitochondria during Aging.Antioxidants (Basel, Switzerland) · 2020Article
- Requirement for Serine-384 in Caspase-2 processing and activity.Cell death & disease · 2020Article
- Phosphorylation-mediated activation of mouse Xkr8 scramblase for phosphatidylserine exposure.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Active site-adjacent phosphorylation at Tyr-397 by c-Abl kinase inactivates caspase-9.The Journal of biological chemistry · 2017Article
- Evaluation of protein kinase CK2 as a therapeutic target for squamous cell carcinoma of cats.American journal of veterinary research · 2017Article
- Caspase-9: structure, mechanisms and clinical application.Oncotarget · 2017Review
- Dual Site Phosphorylation of Caspase-7 by PAK2 Blocks Apoptotic Activity by Two Distinct Mechanisms.Structure (London, England : 1993) · 2017Article
- Protein kinase CK2 inhibition induces cell death via early impact on mitochondrial function.Journal of cellular biochemistry · 2014Article
- Regulation of the proapoptotic functions of prostate apoptosis response-4 (Par-4) by casein kinase 2 in prostate cancer cells.Cell death & disease · 2014Article
- Cellular mechanisms controlling caspase activation and function.Cold Spring Harbor perspectives in biology · 2013Review
- Protein kinase CK2 is a critical regulator of epithelial homeostasis in chronic intestinal inflammation.Mucosal immunology · 2013Article
- Phosphorylation of the transcription factor YY1 by CK2α prevents cleavage by caspase 7 during apoptosis.Molecular and cellular biology · 2012Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Previous studies from our laboratory had indicated that cytochrome c-independent processing and activation of caspase-9 by caspase-8 contributed to early amplification of the caspase cascade in tumor necrosis factor (TNF)-alpha-treated murine cells. Here we show that murine caspase-9 is phosphorylated by casein kinase 2 (CK2) on a serine near the site of caspase-8 cleavage. CK2 has been shown to regulate cleavage of the pro-apoptotic Bid protein by phosphorylating serine residues near its caspase-8 cleavage site. Similarly, CK2 modification of Ser(348) on caspase-9 appears to render the protease refractory to cleavage by active caspase-8. This phosphorylation did not affect the ability of caspase-9 to autoprocess. Substitution of Ser(348) abolished phosphorylation but not cleavage, and a phospho-site mutant promoted apoptosis in TNF-alpha-treated caspase-9 knock-out mouse embryo fibroblasts. Furthermore, inhibition of CK2 activity and RNA interference-mediated knockdown of the kinase accelerated caspase-9 activation, whereas phosphatase inhibition delayed both caspase-9 activation and death in response to TNF receptor occupation. Taken together, these studies show that TNF receptor cross-linking promotes dephosphorylation of caspase-9, rendering it susceptible to processing by activated caspase-8 protein. Thus, our data suggest that modification of procaspase-9 to protect it from inappropriate cleavage and activation is yet another mechanism by which the oncogenic kinase CK2 promotes survival.
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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.