ArticleNucleic acids research2013
p38 MAPK- and Akt-mediated p300 phosphorylation regulates its degradation to facilitate nucleotide excision repair.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- Synthetic rescue of Xeroderma Pigmentosum C phenotype via PIK3C3 downregulation.Cell death & disease · 2024Article
- p300 nucleocytoplasmic shuttling underlies mTORC1 hyperactivation in Hutchinson-Gilford progeria syndrome.Nature cell biology · 2024Article
- ATF6-Mediated Signaling Contributes to PARP Inhibitor Resistance in Ovarian Cancer.Molecular cancer research : MCR · 2023Article
- Revisiting the Function of p21International journal of molecular sciences · 2022Review
- Nucleotide excision repair leaves a mark on chromatin: DNA damage detection in nucleosomes.Cellular and molecular life sciences : CMLS · 2021Review
- Article
- Xeroderma Pigmentosum C: A Valuable Tool to Decipher the Signaling Pathways in Skin Cancers.Oxidative medicine and cellular longevity · 2021Review
- Endocrine disrupting chemicals may deregulate DNA repair through estrogen receptor mediated seizing of CBP/p300 acetylase.Journal of endocrinological investigation · 2020Review
- Nuclear P38: Roles in Physiological and Pathological Processes and Regulation of Nuclear Translocation.International journal of molecular sciences · 2020Review
- Blocking elevated p38 MAPK restores efferocytosis and inflammatory resolution in the elderly.Nature immunology · 2020Article
- IL-1 Transcriptional Responses to Lipopolysaccharides Are Regulated by a Complex of RNA Binding Proteins.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Germline or inducible knockout of p300 or CBP in skeletal muscle does not alter insulin sensitivity.American journal of physiology. Endocrinology and metabolism · 2019Article
- Signaling Pathways, Chemical and Biological Modulators of Nucleotide Excision Repair: The Faithful Shield against UV Genotoxicity.Oxidative medicine and cellular longevity · 2019Review
- Arid5a Regulation and the Roles of Arid5a in the Inflammatory Response and Disease.Frontiers in immunology · 2019Review
- Review
- Proteasomal degradation of the histone acetyl transferase p300 contributes to beta-cell injury in a diabetes environment.Cell death & disease · 2018Article
- CREBBP and p300 lysine acetyl transferases in the DNA damage response.Cellular and molecular life sciences : CMLS · 2018Review
- And yet, it moves: nuclear and chromatin dynamics of a heterochromatic double-strand break.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
- TLR4-induced NF-κB and MAPK signaling regulate the IL-6 mRNA stabilizing protein Arid5a.Nucleic acids research · 2017Article
- Transcriptional and Posttranslational Regulation of Nucleotide Excision Repair: The Guardian of the Genome against Ultraviolet Radiation.International journal of molecular sciences · 2016Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Besides the primary histone acetyltransferase (HAT)-mediated chromatin remodeling function, co-transcriptional factor, p300, is also known to play a distinct role in DNA repair. However, the exact mechanism of p300 function in DNA repair has remained unclear and difficult to discern due to the phosphorylation and degradation of p300 in response to DNA damage. Here, we have demonstrated that p300 is only degraded in the presence of specific DNA lesions, which are the substrates of nucleotide excision repair (NER) pathway. In contrast, DNA double-strand breaks fail to degrade p300. Degradation is initiated by phosphorylation of p300 at serine 1834, which is catalyzed by the cooperative action of p38 mitogen-activated protein kinases and Akt kinases. In depth, functional analysis revealed that (i) p300 and CBP act redundantly in repairing ultraviolet (UV) lesions, (ii) the phosphorylation of p300 at S1834 is critical for efficient removal of UV-induced cyclobutane pyrimidine dimers and (iii) p300 is recruited to DNA damage sites located within heterochromatin. Taken together, we conclude that phosphorylated p300 initially acetylates histones to relax heterochromatin to allow damage recognition factors access to damage DNA. Thereupon, p300 is promptly degraded to allow the sequential recruitment of downstream repair proteins for successful execution of NER.
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Registered trials
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.