{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:22:57Z","timestamp":1777612977111,"version":"3.51.4"},"reference-count":40,"publisher":"Proceedings of the National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,4,10]]},"abstract":"<jats:p>\n            The cyclin-dependent kinase inhibitor p21\n            <jats:sup>(WAF1\/CIP1)<\/jats:sup>\n            inhibits proliferation both\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in\n vivo<\/jats:italic>\n            , and overexpression of p21 in normal and tumor cell lines\n results in cell cycle arrest. In contrast, ectopic expression of Myc\n alleviates G\n            <jats:sub>1<\/jats:sub>\n            cell cycle arrest. Recent studies showed that\n Myc can repress p21 transcription, thereby overriding a p21-mediated\n cell cycle checkpoint. We found that activation of a Myc-estrogen\n receptor fusion protein by 4-hydroxytamoxifen in mouse cells resulted\n in suppression of endogenous p21 transcription. This effect\n was observed in the absence of\n            <jats:italic>de novo<\/jats:italic>\n            protein synthesis\n and was independent of histone deacetylase activity. In transient\n transfection studies, Myc effectively repressed p21 promoter constructs\n containing only 119 bp of sequence upstream of the transcription start\n site. This region contains multiple Sp1-binding sites and a potential\n initiator element, but no canonical Myc DNA-binding sites. Deletion of\n the potential initiator element does not affect repression of the p21\n promoter by c-Myc. Coimmunoprecipitation and glutathione\n            <jats:italic>S<\/jats:italic>\n            -transferase pull-down experiments demonstrate that\n c-Myc may form complexes with Sp1\/Sp3. We found that the central\n region of c-Myc interacts with the zinc finger domain of Sp1. Because\n Sp1 is required for p21 transcription, it is possible that Myc may\n down-regulate p21 transcription, at least in part, by sequestering Sp1.\n Repression of the p21 promoter may contribute to the ability of c-Myc\n to promote cell proliferation.\n          <\/jats:p>","DOI":"10.1073\/pnas.081074898","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:44:19Z","timestamp":1027694659000},"page":"4510-4515","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":354,"title":["Myc represses the p21\n            <sup>(WAF1\/CIP1)<\/sup>\n            promoter and interacts with Sp1\/Sp3"],"prefix":"10.1073","volume":"98","author":[{"given":"Andrei L.","family":"Gartel","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, University of Illinois College of\r Medicine, Chicago, IL 60607"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Illinois College of\r Medicine, Chicago, IL 60607"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene","family":"Goufman","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Illinois College of\r Medicine, Chicago, IL 60607"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavel","family":"Shianov","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Illinois College of\r Medicine, Chicago, IL 60607"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nissim","family":"Hay","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Illinois College of\r Medicine, Chicago, IL 60607"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feridoon","family":"Najmabadi","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Illinois College of\r Medicine, Chicago, IL 60607"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela L.","family":"Tyner","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Illinois College of\r Medicine, Chicago, IL 60607"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"341","published-online":{"date-parts":[[2001,3,27]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.16.1.653"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb07929.x"},{"key":"e_1_3_3_3_2","first-page":"879","volume":"4","author":"Wagner A J","year":"1993","unstructured":"A J Wagner, C Meyers, L A Laimins, N Hay Cell Growth Differ 4, 879\u2013883 (1993).","journal-title":"Cell Growth Differ"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/382511a0"},{"key":"e_1_3_3_5_2","first-page":"57","volume":"4","author":"Reisman D","year":"1993","unstructured":"D Reisman, N B Elkind, B Roy, J Beamon, V Rotter Cell Growth Differ 4, 57\u201365 (1993).","journal-title":"Cell Growth Differ"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1999.4686"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.13.6635"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201138"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.24.12886"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.9.5913"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90499-G"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/366701a0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90500-P"},{"key":"e_1_3_3_14_2","first-page":"1169","volume":"54","author":"El-Deiry W S","year":"1994","unstructured":"W S El-Deiry, W J Harper, P M O'Connor, V E Velculescu, C E Canman, J Jackman, J A Pietenpol, M Burrell, D E Hill, Y Wang, et al. 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