{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:36:10Z","timestamp":1781102170393,"version":"3.54.1"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,3,17]]},"abstract":"<jats:p>\n                    The expression of ASPP2 (53BP2L), a proapoptotic member of a family of p53-binding proteins, is frequently suppressed in many human cancers. Accumulating evidence suggests that ASPP2 inhibits tumor growth; however, the mechanisms by which ASPP2 suppresses tumor formation remain to be clarified. To study this, we targeted the\n                    <jats:italic>ASPP2<\/jats:italic>\n                    allele in a mouse by replacing exons 10\u201317 with a\n                    <jats:italic>neoR<\/jats:italic>\n                    gene.\n                    <jats:italic>ASPP2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice were not viable because of an early embryonic lethal event. Although\n                    <jats:italic>ASPP2<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice appeared developmentally normal, they displayed an increased incidence of a variety of spontaneous tumors as they aged. Moreover, \u03b3-irradiated 6-week-old\n                    <jats:italic>ASPP2<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice developed an increased incidence of high-grade T cell lymphomas of thymic origin compared with\n                    <jats:italic>ASPP2<\/jats:italic>\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice. Primary thymocytes derived from\n                    <jats:italic>ASPP2<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice exhibited an attenuated apoptotic response to \u03b3-irradiation compared with\n                    <jats:italic>ASPP2<\/jats:italic>\n                    <jats:sup>+\/+<\/jats:sup>\n                    thymocytes. Additionally,\n                    <jats:italic>ASPP2<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    primary mouse embryonic fibroblasts demonstrated a defective G\n                    <jats:sub>0<\/jats:sub>\n                    \/G\n                    <jats:sub>1<\/jats:sub>\n                    cell cycle checkpoint after \u03b3-irradiation. Our results demonstrate that ASPP2 is a haploinsufficient tumor suppressor and, importantly, open new avenues for investigation into the mechanisms by which disruption of ASPP2 pathways could play a role in tumorigenesis and response to therapy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0809080106","type":"journal-article","created":{"date-parts":[[2009,2,26]],"date-time":"2009-02-26T21:45:45Z","timestamp":1235684745000},"page":"4390-4395","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":46,"title":["Apoptosis-stimulating protein of p53 (ASPP2) heterozygous mice are tumor-prone and have attenuated cellular damage\u2013response thresholds"],"prefix":"10.1073","volume":"106","author":[{"given":"Kerstin M.","family":"Kampa","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97239;"},{"name":"Medizinsche Universit\u00e4tsklinik, Department of Hematology, Oncology, Rheumatology, Immunology, and Pulmology, Universit\u00e4t T\u00fcbingen, T\u00fcbingen 72076, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared D.","family":"Acoba","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97239;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dexi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97239;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Gay","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97239;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunjoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97239;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Beemer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97239;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emerson","family":"Padiernos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97239;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataya","family":"Boonmark","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, Division of Hematology and Oncology, Stanford University, Stanford, CA 94305; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97239;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice C.","family":"Fan","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, Division of Hematology and Oncology, Stanford University, Stanford, CA 94305; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis S.","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97239;"},{"name":"Oregon Stem Cell Center, Portland, OR 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Fleming","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97239;"},{"name":"Oregon Stem Cell Center, Portland, OR 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Corless","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97239;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean W.","family":"Felsher","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, Division of Hematology and Oncology, Stanford University, Stanford, CA 94305; 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