{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:09:51Z","timestamp":1770336591206,"version":"3.49.0"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,8,6]],"date-time":"2003-08-06T00:00:00Z","timestamp":1060128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2003,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although ATM, the protein defective in ataxia\u2010telangiectasia (A\u2010T), is activated primarily by radiation, there is also evidence that expression of the protein can be regulated by both radiation and growth factors. Computer analysis of the <jats:italic>ATM<\/jats:italic> promoter proximal 700\u2010bp sequence reveals a number of potentially important <jats:italic>cis<\/jats:italic>\u2010regulatory sequences. Using nucleotide substitutions to delete putative functional elements in the promoter of <jats:italic>ATM<\/jats:italic>, we examined the importance of some of these sites for both the basal and the radiation\u2010induced activity of the promoter. In lymphoblastoid cells, most of the mutations in transcription factor consensus sequences [Sp1(1), Sp1(2), Cre, Ets, Xre, \u03b3Ire(2), a modified AP1 site (Fse), and GCF] reduced basal activity to various extents, whereas others [\u03b3Ire(1), NF1, Myb] left basal activity unaffected. In human skin fibroblasts, results were generally the same, but the basal activity varied up to 8\u2010fold in these and other cell lines. Radiation activated the promoter approximately 2.5\u2010fold in serum\u2010starved lymphoblastoid cells, reaching a maximum by 3 hr, and all mutated elements equally blocked this activation. Reduction in Sp1 and AP1 DNA binding activity by serum starvation was rapidly reversed by exposure of cells to radiation. This reduction was not evident in A\u2010T cells, and the response to radiation was less marked. Data provided for interaction between ATM and Sp1 by protein binding and co\u2010immunoprecipitation could explain the altered regulation of Sp1 in A\u2010T cells. The data described here provide additional evidence that basal and radiation\u2010induced regulation of the <jats:italic>ATM<\/jats:italic> promoter is under multifactorial control. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.10261","type":"journal-article","created":{"date-parts":[[2003,8,22]],"date-time":"2003-08-22T14:32:57Z","timestamp":1061562777000},"page":"157-167","source":"Crossref","is-referenced-by-count":28,"title":["Site\u2010directed mutagenesis of the <i>ATM<\/i> promoter: Consequences for response to proliferation and ionizing radiation"],"prefix":"10.1002","volume":"38","author":[{"given":"Nuri","family":"Gueven","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Keating","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Fukao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi","family":"Loeffler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. 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