The FBXW7 {beta}-form is suppressed in human glioma cells

Journal Article · Fri Mar 23 04:00:00 EDT 2007 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2007.01.080· OSTI ID:20979846

Gu, Zhaodi ^[1]; Inomata, Kenichi ^[1]; Ishizawa, Kota ^[1]; Horii, Akira ^[1]

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1. Department of Molecular Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575 (Japan)

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 {beta}-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.

• OSTI ID: 20979846
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 354; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ASPARTIC ACID
CARCINOGENESIS
CELL CYCLE
CELL PROLIFERATION
GLIOMAS
HUMAN POPULATIONS
LARGE INTESTINE
LIGASES
MUTATIONS
PROSTATE
TRYPTOPHAN
TUMOR CELLS