{"corpus_id":251776912,"paper_sha":"4f67d8f61a94e11c73ef17cb9c22013d11987517","doi":"10.1016/j.bbrc.2022.08.031","arxiv_id":null,"pmid":36030658,"pmcid":null,"mag_id":null,"dblp_id":null,"acl_id":null,"title":"TRAF2 regulates the protein stability of HIPK2.","year":2022,"publication_date":"2022-08-01","venue":"Biochemical and Biophysical Research Communications - BBRC","journal":{"name":"Biochemical and biophysical research communications","pages":"\n          97-102\n        ","volume":"627"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":26,"citation_count":4,"influential_citation_count":0,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Apoptosis","mj":false,"ui":"D017209"},{"d":"Protein Serine-Threonine Kinases","mj":true,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D017346"},{"d":"Protein Stability","mj":false,"ui":"D055550"},{"d":"TNF Receptor-Associated Factor 2","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D047992"},{"d":"Tumor Necrosis Factor-alpha","mj":true,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D014409"},{"d":"Ubiquitin-Protein Ligases","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D044767"}],"chemicals":[{"n":"TNF Receptor-Associated Factor 2","ui":"D047992","reg":"0"},{"n":"Tumor Necrosis Factor-alpha","ui":"D014409","reg":"0"},{"n":"Ubiquitin-Protein Ligases","ui":"D044767","reg":"EC 2.3.2.27"},{"n":"Protein Serine-Threonine Kinases","ui":"D017346","reg":"EC 2.7.11.1"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"A nuclear serine/threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) is a critical regulator of development and DNA damage response. HIPK2 can induce apoptosis under cellular stress conditions and thus its protein level is maintained low by constant proteasomal degradation. In the present study, we present evidence that TNF receptor-associated factor 2 (TRAF2) regulates the protein stability of HIPK2. Overexpression of TRAF2 decreased while its knockdown increased the HIPK2 protein level. The TRAF2-mediated decrease in HIPK2 protein expression was blocked by proteasomal inhibitor. In addition, TRAF2 decreased the protein half-life of HIPK2. We found that HIPK2 and TRAF2 co-immunoprecipitated. Interestingly, the co-immunoprecipitation was reduced while HIPK2 protein level increased following TNFα treatment, suggesting TNFα induced dissociation of TRAF2 from HIPK2 to accumulate HIPK2. Inhibition of HIPK2 partially suppressed TNFα-induced cell death, indicating that the accumulated HIPK2 may contribute to the TNFα-induced cell death. Our results suggest that TRAF2 can regulate proapoptotic function of HIPK2 by promoting proteasomal degradation.","claims":[{"public_id":"cl_ad1dc801f5603a0d943623fc1debd9ad","status":"active","text":"A proteasomal inhibitor blocks the TRAF2-mediated decrease in HIPK2 protein expression.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_ad1dc801f5603a0d943623fc1debd9ad"},{"public_id":"cl_fee5f182a874fa89e6b5961bb6e687f1","status":"active","text":"TNFα induces dissociation of TRAF2 from HIPK2, leading to HIPK2 accumulation and contributing to TNFα-induced cell death.","confidence":0.93,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_fee5f182a874fa89e6b5961bb6e687f1"},{"public_id":"cl_9e926bce09d42432cfd7bbc083c03223","status":"active","text":"TRAF2 decreases the protein half-life of HIPK2 and physically associates with HIPK2 in co-immunoprecipitation assays.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_9e926bce09d42432cfd7bbc083c03223"},{"public_id":"cl_ad948ece9b57e8b3c4451eca756e59b6","status":"active","text":"TRAF2 overexpression decreases HIPK2 protein levels, whereas TRAF2 knockdown increases HIPK2 protein levels.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_ad948ece9b57e8b3c4451eca756e59b6"},{"public_id":"cl_36eed38398ceffc294502d7b6372ddf5","status":"active","text":"TRAF2 regulates HIPK2 protein stability by promoting its proteasomal degradation.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_36eed38398ceffc294502d7b6372ddf5"}],"concepts":[{"public_id":"co_4377a35a7a9e61aad577d103c4e78a44","status":"active","name":"proteasomal inhibitor","description":"A compound that blocks proteasome-dependent protein degradation.","types":["chemical inhibitor"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_4377a35a7a9e61aad577d103c4e78a44"},{"public_id":"co_51d50df0536852ec3efe2b99d38954bb","status":"active","name":"apoptosis","description":"Programmed cell death promoted by HIPK2 under cellular stress.","types":["cell death process"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_51d50df0536852ec3efe2b99d38954bb"},{"public_id":"co_60fc4342462f8e2960565a99fa4420f5","status":"active","name":"co-immunoprecipitation","description":"An assay used to detect physical association between proteins.","types":["assay"],"aliases":["co-IP"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_60fc4342462f8e2960565a99fa4420f5"},{"public_id":"co_84943c2fc41def19d631204a6aaba99f","status":"active","name":"protein half-life","description":"The time required for half of a protein population to be degraded.","types":["measurement"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_84943c2fc41def19d631204a6aaba99f"},{"public_id":"co_aa2c2751e734e314b175eae38ce5caa7","status":"active","name":"TNFα","description":"Tumor necrosis factor alpha, a cytokine used here to trigger HIPK2 accumulation and cell death.","types":["cytokine"],"aliases":["tumor necrosis factor alpha","TNF-alpha"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_aa2c2751e734e314b175eae38ce5caa7"},{"public_id":"co_b21c86fa2f32a108f838a689a3f4c534","status":"active","name":"proteasomal degradation","description":"Protein breakdown mediated by the proteasome.","types":["molecular process"],"aliases":["proteasome-mediated degradation"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_b21c86fa2f32a108f838a689a3f4c534"},{"public_id":"co_b456934213801f5a63fae39d69b6545b","status":"active","name":"TRAF2","description":"TNF receptor-associated factor 2, a signaling adaptor protein that interacts with HIPK2 in this study.","types":["protein"],"aliases":["TNF receptor-associated factor 2"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_b456934213801f5a63fae39d69b6545b"},{"public_id":"co_b4a2dc500b91668e33532d4c495d6d32","status":"active","name":"HIPK2","description":"Homeodomain-interacting protein kinase 2, a nuclear serine/threonine kinase involved in stress-induced apoptosis and DNA damage response.","types":["protein","kinase"],"aliases":["homeodomain-interacting protein kinase 2"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_b4a2dc500b91668e33532d4c495d6d32"},{"public_id":"co_d853b1f566d0acd56db4edb1e9ee7eca","status":"active","name":"cell death","description":"Loss of cell viability measured as an outcome of TNFα treatment.","types":["outcome"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_d853b1f566d0acd56db4edb1e9ee7eca"},{"public_id":"co_ddecb43a36296b131de88d1fae906793","status":"active","name":"overexpression","description":"Experimental increase in the cellular level of a gene or protein.","types":["experimental manipulation"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_ddecb43a36296b131de88d1fae906793"}],"external_ids":{"DOI":"10.1016/j.bbrc.2022.08.031","ArXiv":null,"PubMed":36030658,"PubMedCentral":null,"MAG":null,"DBLP":null,"ACL":null},"open_access":{"is_open_access":false,"pdf_url":null,"landing_url":"https://sah.borca.ai/papers/251776912","source":null,"pdf_url_source":null,"license":null,"reason":"pdf_url_not_indexed"},"reference_availability":{"status":"available","references_indexed":true,"full_text_available":false,"full_text_source":null,"count_basis":"semantic_scholar_metadata","extraction_status":"not_applicable","reason":null},"source":{"provider":"episteme2","base_corpus":"semantic_scholar_dump","freshness_mode":"unknown","basis":["semantic_scholar_metadata","postgres_metadata"],"limits":["paper metadata is based on indexed upstream scholarly datasets","claims and concepts are available only for extracted papers","absence of claims or concepts means no extracted graph data is available in this response"],"status":"available","degraded":false,"degraded_reasons":[],"diagnostics":{"status":"available","degraded":false,"degraded_reasons":[],"metadata_status":"available","graph_status":"available","abstract_status":"available"},"source_flags":5},"paper_id":631527,"paper_uid":"ba6e8783-ea30-45d5-90ac-1870d0ec0ecd","canonical_identity":{"paper_id":631527,"paper_uid":"ba6e8783-ea30-45d5-90ac-1870d0ec0ecd","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/251776912"}