FBXW7 influences murine intestinal homeostasis and cancer, targeting Notch, Jun, and DEK for degradation

• DOI: 10.1084/jem.20100830
• Publication Date: 2011-02-01T03:24:37Z
• Authors: Roya Babaei-Jadidi; Ningning Li; Anas Saadeddin; Bradley Spencer-Dene; Anett Jandke; Belal Muhammad; ElSayed E. Ibrahim; Ranjithmenon Mura...; Mohammed Abuzinadah; Hayley Davis; Annabelle Lewis; Susan Watson; Axel Behrens; Ian Tomlinson; Abdolrahman Shams...
• Keywords: Homeostasis; Degradation

The Fbxw7 (F-box/WD repeat–containing protein 7; also called CDC4, Sel10, Ago, and Fbw7) component of the SCF (Skp1/Cullin/F-box protein) E3 ubiquitin ligase complex acts as a tumor suppressor in several tissues targets multiple transcriptional activators protooncogenes for ubiquitin-mediated degradation. To understand function murine intestine, this study, we specifically deleted gut using Villin-Cre (Fbxw7ΔG). In wild-type mice, loss altered homeostasis intestinal epithelium, resulted elevated Notch c-Jun expression, induced development adenomas at 9–10 mo age. context APC (adenomatous polyposis coli) deficiency (ApcMin/+ mice), accelerated tumorigenesis death promoted accumulation β-catenin late but not early time points. At points, mutant tumors showed DEK protooncogene. expression cell division splicing tropomyosin (TPM) RNA, which may influence proliferation. TPM RNA were detected FBXW7 human colorectal tissues. Given their reduced lifespan increased incidence tumors, ApcMin/+Fbxw7ΔG mice be used testing carcinogenicity drug screening.