ArticlePloS one2012
CDK2 and PKA mediated-sequential phosphorylation is critical for p19INK4d function in the DNA damage response.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Tumour endothelial cell reprogramming orchestrates angiocrine signalling to drive chemoresistance in breast cancer.Angiogenesis · 2026Article
- Phosphoregulation of RAD51AP1 function in homology-directed repair.bioRxiv : the preprint server for biology · 2025Article
- CIP/KIP and INK4 families as hostages of oncogenic signaling.Cell division · 2024Review
- INK4 cyclin-dependent kinase inhibitors as potential prognostic biomarkers and therapeutic targets in hepatocellular carcinoma.Bioscience reports · 2022Article
- Article
- The Human Papillomavirus E6 PDZ Binding Motif Links DNA Damage Response Signaling to E6 Inhibition of p53 Transcriptional Activity.Journal of virology · 2018Article
- Phosphorylation-induced unfolding regulates p19Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Structural prediction of the interaction of the tumor suppressor p27BMC bioinformatics · 2017Article
- Reversible p53 inhibition prevents cisplatin ototoxicity without blocking chemotherapeutic efficacy.EMBO molecular medicine · 2017Article
- A mechanism of global shape-dependent recognition and phosphorylation of filamin by protein kinase A.The Journal of biological chemistry · 2015Article
- Role of p19ink4d in the pathogenesis of hearing loss.International journal of clinical and experimental pathology · 2015Article
- Nuclear translocation of p19INK4d in response to oxidative DNA damage promotes chromatin relaxation.Molecular and cellular biochemistry · 2015Article
- RETRACTED: PKA-mediated phosphorylation of ATR promotes recruitment of XPA to UV-induced DNA damage.Molecular cell · 2014Article
- p19(INK4d) mRNA and protein expression as new prognostic factors in ovarian cancer patients.Cancer biology & therapy · 2013Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA damage triggers a phosphorylation-based signaling cascade known as the DNA damage response. p19INK4d, a member of the INK4 family of CDK4/6 inhibitors, has been reported to participate in the DNA damage response promoting DNA repair and cell survival. Here, we provide mechanistic insight into the activation mechanism of p19INK4d linked to the response to DNA damage. Results showed that p19INK4d becomes phosphorylated following UV radiation, β-amyloid peptide and cisplatin treatments. ATM-Chk2/ATR-Chk1 signaling pathways were found to be differentially involved in p19INK4d phosphorylation depending on the type of DNA damage. Two sequential phosphorylation events at serine 76 and threonine 141 were identified using p19INK4d single-point mutants in metabolic labeling assays with (32)P-orthophosphate. CDK2 and PKA were found to participate in p19INK4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Nuclear translocation of p19INK4d induced by DNA damage was shown to be dependent on serine 76 phosphorylation. Most importantly, both phosphorylation sites were found to be crucial for p19INK4d function in DNA repair and cell survival. In contrast, serine 76 and threonine 141 were dispensable for CDK4/6 inhibition highlighting the independence of p19INK4d functions, in agreement with our previous findings. These results constitute the first description of the activation mechanism of p19INK4d in response to genotoxic stress and demonstrate the functional relevance of this activation following DNA damage.
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