{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T19:43:54Z","timestamp":1777491834003,"version":"3.51.4"},"reference-count":30,"publisher":"Proceedings of the National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,4,29]]},"abstract":"<jats:p>The tumor suppressor p53 is regulated in part by binding to cellular proteins. We used p53 as bait in the yeast two-hybrid system and isolated homeodomain-interacting protein kinase 1 (HIPK1) as a p53-binding protein. Deletion analysis showed that amino acids 100\u2013370 of p53 and amino acids 885-1093 of HIPK1 were sufficient for HIPK1\u2013p53 interaction. HIPK1 was capable of autophosphorylation and specific serine phosphorylation of p53. The<jats:italic>HIPK1<\/jats:italic>gene was highly expressed in human breast cancer cell lines and oncogenically transformed mouse embryonic fibroblasts.<jats:italic>HIPK1<\/jats:italic>was localized to human chromosome band 1p13, a site frequently altered in cancers. Gene-targeted<jats:italic>HIPK1<\/jats:italic>\u2212\/\u2212 mice were grossly normal but oncogenically transformed<jats:italic>HIPK1<\/jats:italic>\u2212\/\u2212 mouse embryonic fibroblasts exhibited reduced transcription of<jats:italic>Mdm2<\/jats:italic>and were more susceptible than transformed<jats:italic>HIPK1<\/jats:italic>+\/+ cells to apoptosis induced by DNA damage. Carcinogen-treated<jats:italic>HIPK1<\/jats:italic>\u2212\/\u2212 mice developed fewer and smaller skin tumors than<jats:italic>HIPK1<\/jats:italic>+\/+ mice. HIPK1 may thus play a role in tumorigenesis, perhaps by means of the regulation of p53 and\/or Mdm2.<\/jats:p>","DOI":"10.1073\/pnas.0530308100","type":"journal-article","created":{"date-parts":[[2003,4,29]],"date-time":"2003-04-29T16:23:56Z","timestamp":1051633436000},"page":"5431-5436","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":64,"title":["Characterization of cells and gene-targeted mice deficient for the p53-binding kinase homeodomain-interacting protein kinase 1 (HIPK1)"],"prefix":"10.1073","volume":"100","author":[{"given":"Seiji","family":"Kondo","sequence":"first","affiliation":[{"name":"Advanced Medical Discovery Institute, 620 University Avenue, Suite 707, Toronto, ON, Canada M5G 2C1; Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2C1; Amgen Inc., Thousand Oaks, CA 91320-1789; and Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Lu","sequence":"additional","affiliation":[{"name":"Advanced Medical Discovery Institute, 620 University Avenue, Suite 707, Toronto, ON, Canada M5G 2C1; 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