{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liebl MC"],"funding":["Deutsche Forschungsgemeinschaft"],"pagination":["2759-2776"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7969023"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["49(5)"],"pubmed_abstract":["The DNA damage-responsive tumor suppressors p53 and HIPK2 are well established regulators of cell fate decision-making and regulate the cellular sensitivity to DNA-damaging drugs. Here, we identify Deleted in Azoospermia-associated protein 2 (DAZAP2), a small adaptor protein, as a novel regulator of HIPK2 and specifier of the DNA damage-induced p53 response. Knock-down or genetic deletion of DAZAP2 strongly potentiates cancer cell chemosensitivity both in cells and in vivo using a mouse tumour xenograft model. In unstressed cells, DAZAP2 stimulates HIPK2 polyubiquitination and degradation through interplay with the ubiquitin ligase SIAH1. Upon DNA damage, HIPK2 site-specifically phosphorylates DAZAP2, which terminates its HIPK2-degrading function and triggers its re-localization to the cel"],"journal":["Nucleic acids research"],"pubmed_title":["DAZAP2 acts as specifier of the p53 response to DNA damage."],"pmcid":["PMC7969023"],"funding_grant_id":["SFB 1361","SFB 1036"],"pubmed_authors":["Abdeen SK","Raddatz G","Liebl MC","Becker H","Aqeilan RI","Moehlenbrink J","Hofmann TG","Lyko F"],"additional_accession":[]},"is_claimable":false,"name":"DAZAP2 acts as specifier of the p53 response to DNA damage.","description":"The DNA damage-responsive tumor suppressors p53 and HIPK2 are well established regulators of cell fate decision-making and regulate the cellular sensitivity to DNA-damaging drugs. Here, we identify Deleted in Azoospermia-associated protein 2 (DAZAP2), a small adaptor protein, as a novel regulator of HIPK2 and specifier of the DNA damage-induced p53 response. Knock-down or genetic deletion of DAZAP2 strongly potentiates cancer cell chemosensitivity both in cells and in vivo using a mouse tumour xenograft model. In unstressed cells, DAZAP2 stimulates HIPK2 polyubiquitination and degradation through interplay with the ubiquitin ligase SIAH1. Upon DNA damage, HIPK2 site-specifically phosphorylates DAZAP2, which terminates its HIPK2-degrading function and triggers its re-localization to the cel","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2026-05-01T17:28:48.87Z","creation":"2024-11-13T06:29:03.4Z"},"accession":"S-EPMC7969023","cross_references":{"pubmed":["33591310"],"doi":["10.1093/nar/gkab084"]}}