Rsearch led by Dr Abdolrahman Shams-Nateri of the Division of Pre-Clinical Oncology has been published in the leading Journal of Experimental Medicine.
In this study, the investigators reported that the Fbxw7 inactivation induces adenomas and addressed detailed molecular mechanisms of Fbxw7 tumour suppressor activity in the conditional knockout of Fbxw7 mouse intestine. They identified the proto-oncogene DEK as a novel target of Fbxw7-E3 ligase activity that changes alternative RNA splicing of tropomyosin (TPM) isoforms. Fbxw7 inactivation impairs degradation of the DEK proto-oncogene and leads to specific loss of the epithelial isoform of TPM, which, cooperatively with Notch and Jun, contributes to carcinogenesis in mice.
Reference:
FBXW7 influences murine intestinal homeostasis and cancer, targeting Notch, Jun, and DEK for degradation.
Babaei-Jadidi R, Li N, Saadeddin A, Spencer-Dene B, Jandke A, Muhammad B, Ibrahim EE, Muraleedharan R, Abuzinadah M, Davis H, Lewis A, Watson S, Behrens A, Tomlinson I, Nateri AS. J Exp Med. 2011 Feb 14;208(2):295-312.