TAILIEUCHUNG - Báo cáo Y học: Antiproliferative proteins of the BTG/Tob family are degraded by the ubiquitin-proteasome system

BTG/Tob family proteins, which are characterized by similarities in their N-terminal 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–proteasome 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. | Eur. J. Biochem. 269 3596-3604 2002 FEBS 2002 doi Antiproliferative proteins of the BTG Tob family are degraded by the ubiquitin-proteasome system Hitoshi Sasajima Koji Nakagawa and Hideyoshi Yokosawa Department of Biochemistry Graduate School of Pharmaceutical Sciences Hokkaido University Sapporo Japan BTG Tob family proteins which are characterized by similarities in their N-terminal 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-proteasome 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 protea-some-specific inhibitors. Co-expression of BTG1 BTG2 Tob or Tob2 protein with ubiquitin in HEK293 cells revealed specific multiubiquitination of each of the four proteins. Although the full-length and N-terminal truncated forms of BTG1 BTG2 Tob and Tob2 proteins were unstable the respective C-terminal truncated forms were found to be almost stable suggesting that the C-terminal regions control the stabilities of BTG1 BTG2 Tob and Tob2 proteins. In addition it was found that the respective C-terminal regions confer instability on green fluorescent protein a normally stable protein. Thus it can be concluded that the C-terminal regions are necessary and sufficient to control the stabilities of BTG1 BTG2 Tob and Tob2 proteins. Keywords BTG Tob ubiquitin proteasome degradation signal. The BTG Tob family is composed of at least six distinct members in vertebrates namely BTG1 BTG2 TIS21 PC3 BTG3 ANA PC3B Tob and Tob2 1 . The main characteristic of this family is the .

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