Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7

Masayoshi Yada, Shigetsugu Hatakeyama, Takumi Kamura, Masaaki Nishiyama, Ryosuke Tsunematsu, Hiroyuki Imaki, Noriko Ishida, Fumihiko Okumura, Keiko Nakayama, Keiichi I. Nakayama

研究成果: ジャーナルへの寄稿記事

486 引用 (Scopus)

抜粋

The F-box protein Skp2 mediates c-Myc ubiquitylation by binding to the MB2 domain. However, the turnover of c-Myc is largely dependent on phosphorylation of threonine-58 and serine-62 in MB1, residues that are often mutated in cancer. We now show that the F-box protein Fbw7 interacts with and thereby destabilizes c-Myc in a manner dependent on phosphorylation of MB1. Whereas wild-type Fbw7 promoted c-Myc turnover in cells, an Fbw7 mutant lacking the F-box domain delayed it. Furthermore, depletion of Fbw7 by RNA interference increased both the abundance and transactivation activity of c-Myc. Accumulation of c-Myc was also apparent in mouse Fbw7-1- embryonic stem cells. These observations suggest that two F-box proteins, Fbw7 and Skp2, differentially regulate c-Myc stability by targeting MB1 and MB2, respectively.

元の言語英語
ページ(範囲)2116-2125
ページ数10
ジャーナルEMBO Journal
23
発行部数10
DOI
出版物ステータス出版済み - 5 19 2004

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

これを引用

Yada, M., Hatakeyama, S., Kamura, T., Nishiyama, M., Tsunematsu, R., Imaki, H., ... Nakayama, K. I. (2004). Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO Journal, 23(10), 2116-2125. https://doi.org/10.1038/sj.emboj.7600217