{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T11:37:40Z","timestamp":1772365060192,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2002,7,19]],"date-time":"2002-07-19T00:00:00Z","timestamp":1027036800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Biochemistry"],"published-print":{"date-parts":[[2002,7]]},"abstract":"<jats:p>BTG\/Tob family proteins, which are characterized by similarities in their N\u2010terminal BTG\/Tob homology domains, control cell growth negatively. Among the BTG\/Tob family members, BTG2\/TIS21\/PC3 proteins have been reported to have short lives and to be degraded by the proteasome. However, the mechanisms regulating the stabilities of other BTG\/Tob family proteins have not yet been clarified. Here, we report that BTG1, Tob, and Tob2 proteins, as well as BTG2 protein, are degraded by the ubiquitin\u2013proteasome system; the degradation of Tob protein in HeLa cells and the degradation of BTG1, BTG2, Tob and Tob2 proteins transiently expressed in HEK293 cells were inhibited by treatments with proteasome\u2010specific inhibitors. Co\u2010expression of BTG1, BTG2, Tob, or Tob2 protein with ubiquitin in HEK293 cells revealed specific multiubiquitination of each of the four proteins. Although the full\u2010length and N\u2010terminal truncated forms of BTG1, BTG2, Tob, and Tob2 proteins were unstable, the respective C\u2010terminal truncated forms were found to be almost stable, suggesting that the C\u2010terminal regions control the stabilities of BTG1, BTG2, Tob, and Tob2 proteins. In addition, it was found that the respective C\u2010terminal regions confer instability on green fluorescent protein, a normally stable protein. Thus, it can be concluded that the C\u2010terminal regions are necessary and sufficient to control the stabilities of BTG1, BTG2, Tob, and Tob2 proteins.<\/jats:p>","DOI":"10.1046\/j.1432-1033.2002.03052.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T18:32:52Z","timestamp":1047407572000},"page":"3596-3604","source":"Crossref","is-referenced-by-count":44,"title":["Antiproliferative proteins of the BTG\/Tob family are degraded by the ubiquitin\u2010proteasome system"],"prefix":"10.1111","volume":"269","author":[{"given":"Hitoshi","family":"Sasajima","sequence":"first","affiliation":[]},{"given":"Koji","family":"Nakagawa","sequence":"additional","affiliation":[]},{"given":"Hideyoshi","family":"Yokosawa","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2002,7,19]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02436-X"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.8.3353"},{"key":"e_1_2_7_4_2","doi-asserted-by":"crossref","first-page":"14511","DOI":"10.1016\/S0021-9258(18)98716-8","article-title":"Structure and expression of TIS21, a primary response gene induced by growth factors and tumor promoters","volume":"266","author":"Fletcher B.S.","year":"1991","journal-title":"J. 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