The FBXW7 β-form is suppressed in human glioma cells

Zhaodi Gu, Kenichi Inomata, Kota Ishizawa, Akira Horii

研究成果: Article査読

23 被引用数 (Scopus)

抄録

FBXW7 (F-box and WD40 domain protein 7) is an F-box protein with 7 tandem WDs (tryptophan-aspartic acid) that functions as a phosphoepitope-specific substrate recognition component of SCF (Skp1-Cul1-F-box protein) ubiquitin ligases and catalyzes the ubiquitination of proteins promoting cell proliferation, such as CCNE1, MYC, AURKA, NOTCH1, and JUN, which are frequently activated in a wide range of human cancers. FBXW7 is a candidate tumor suppressor, and mutations have been reported in some human tumors. In this study, we analyzed 84 human tumor cell lines in search for genetic alterations of FBXW7, as well as mRNA and protein expressional changes, and compared them with expression levels of the CCNE1, MYC, and AURKA proteins. We found a novel nonsense mutation in a colon cancer cell line SCC and confirmed the missense mutations in SKOV3, an ovarian cancer cell line, and LoVo, a colon cancer cell line. Moreover, suppressed expression of FBXW7 accompanied by activation of the target proteins were observed in ovarian, colon, endometrial, gastric, and prostate cancers. It is notable that highly suppressed mRNA expression of the FBXW7 β-form was found in all the human glioma cell lines analyzed; enhanced expressions of CCNE1, MYC, and AURKA were observed in these cells. Our present results imply that FBXW7 plays a pivotal role in many tissues by controlling the amount of cell cycle promoter proteins and that dysfunction of this protein is one of the essential steps in carcinogenesis in multiple organs.

本文言語English
ページ(範囲)992-998
ページ数7
ジャーナルBiochemical and biophysical research communications
354
4
DOI
出版ステータスPublished - 2007 3 23

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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