{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:28:35Z","timestamp":1773289715135,"version":"3.50.1"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2003,4,1]],"date-time":"2003-04-01T00:00:00Z","timestamp":1049155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["www.embopress.org"],"crossmark-restriction":false},"short-container-title":["EMBO Reports"],"published-print":{"date-parts":[[2003,4]]},"abstract":"<jats:p>A diverse range of conditions, from mitogenic stimuli to cytotoxic stress, can induce cell senescence. Here, I propose that simultaneous stimulation of mitogen\u2010activated pathways and downstream inhibition of cyclin\u2010dependent kinases leads, ultimately, to cell senescence. This model distinguishes between two types of growth arrest: first, exit to G0 phase, which is caused by the withdrawal of mitogens and can lead to apoptosis; and second, hypermitogenic arrest, which is stimulated by mitogens and can lead to senescence. The concept of hypermitogenic arrest defines cell senescence as a functionally active, stable and conditionally reversible state.<\/jats:p>","DOI":"10.1038\/sj.embor.embor806","type":"journal-article","created":{"date-parts":[[2003,4,9]],"date-time":"2003-04-09T13:10:48Z","timestamp":1049893848000},"page":"358-362","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":125,"title":["Cell senescence and hypermitogenic arrest"],"prefix":"10.1038","volume":"4","author":[{"given":"Mikhail V","family":"Blagosklonny","sequence":"first","affiliation":[{"name":"Brander Cancer Research Institute, New York Medical College Suite 2400 19 Bradhurst Avenue Hawthorne New York 10532 USA"}]}],"member":"297","published-online":{"date-parts":[[2003,4]]},"reference":[{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.853700a"},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119817"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.21.7385-7397.2002"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19981109)78:4<511::AID-IJC19>3.0.CO;2-8"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.1.2.108"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf289"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/220134a0"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(01)82148-6"},{"key":"e_1_2_3_10_1","first-page":"3761","article-title":"A senescence\u2010like phenotype distinguishes tumor cells that undergo terminal proliferation arrest after exposure to anticancer agents","volume":"59","author":"Chang B.D.","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.1.3.128"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203438"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.1.5.146"},{"key":"e_1_2_3_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010690200"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1317"},{"key":"e_1_2_3_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.8.1931"},{"key":"e_1_2_3_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.3.1611"},{"key":"e_1_2_3_18_1","first-page":"1485","article-title":"Growth imbalance and altered expression of cyclins B1, A, E and D3 in MOLT\u20104 cells synchronized in the cell cycle by inhibitors of DNA replication","volume":"6","author":"Gong J.","year":"1995","journal-title":"Cell Growth Differ."},{"key":"e_1_2_3_19_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.1.4.14"},{"key":"e_1_2_3_20_1","first-page":"5076","article-title":"Constitutive p38HOG mitogen\u2010activated protein kinase activation induces permanent cell cycle arrest and senescence","volume":"62","author":"Haq R.","year":"2002","journal-title":"Cancer Res."},{"key":"e_1_2_3_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.23.3644"},{"key":"e_1_2_3_22_1","first-page":"17","article-title":"Enhanced mitogen\u2010induced proliferation of rat splenocytes by low\u2010dose whole\u2010body X\u2010irradiation","volume":"27","author":"Ishii K.","year":"1995","journal-title":"Physiol. 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