Monoubiquitination of Tob/BTG family proteins competes with degradation-targeting polyubiquitination.

Toru Suzuki, Minsoo Kim, Hiroko Kozuka-Hata, Masato Watanabe, Masaaki Oyama, Kouhei Tsumoto, Tadashi Yamamoto

Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Japan. toru@ims.u-tokyo.ac.jp

Biochemical and biophysical research communications 2011 May 27

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Tob belongs to the anti-proliferative Tob/BTG protein family. The expression level of Tob family proteins is strictly regulated both transcriptionally and through post-translational modification. Ubiquitin (Ub)/proteosome-dependent degradation of Tob family proteins is critical in controlling cell cycle progression and DNA damage responses. Various Ub ligases (E3s) are responsible for degradation of Tob protein. Here, we show that Tob family proteins undergo monoubiquitination even in the absence of E3s in vitro. Determination of the ubiquitination site(s) in Tob by mass spectrometric analysis revealed that two lysine residues (Lys48 and Lys63) located in Tob/BTG homology domain are ubiquitinated. A mutant Tob, in which both Lys48 and Lys63 are substituted with alanine, is more strongly polyubiquitinated than wild-type Tob in vivo. These data suggest that monoubiquitination of Tob family proteins confers resistance against polyubiquitination, which targets proteins for degradation. The strategy for regulating the stability of Tob family proteins suggests a novel role for monoubiquitination. Copyright © 2011 Elsevier Inc. All rights reserved.

Citation

Toru Suzuki, Minsoo Kim, Hiroko Kozuka-Hata, Masato Watanabe, Masaaki Oyama, Kouhei Tsumoto, Tadashi Yamamoto. Monoubiquitination of Tob/BTG family proteins competes with degradation-targeting polyubiquitination. Biochemical and biophysical research communications. 2011 May 27;409(1):70-4