#PROTEIN SCAFFOLD PROTEIN CLIENT SERIES#

Hepatocellular cancer have confirmed the antiproliferative effectĮndometrial adenocarcinoma is the most common With the demonstration that overexpression of CUL5 in T47D breastĬancer cells led to significant suppression of proliferationĬUL5 expression in breast cancer as well as in cervical and

Of the role of CUL5 in cancer cell growth and invasiveness began In numerous important cellular processes including the cell cycle

#PROTEIN SCAFFOLD PROTEIN CLIENT SERIES#

This cascade offers a series of potential interventional steps involving epigenetic modification, miRNA and/or gene targeting and ubiquitination.Ĭullin-5 (CUL5) is a member of the cullin-RING E3 The final step in the cascade may be operating through a decrease in ubiquitination of pro-growth CUL5 ubiquitin ligase clients. These data suggest a cascade in which miR-182 expression is epigenetically increased leading to decreased CUL5 expression and increased cellular proliferation. Finally, we demonstrated for the first time that CUL5 is a direct target of miR-182 that we previously showed to be significantly overexpressed in endometrial adenocarcinomas and we provided evidence that increased miR-182 expression is, at least in part, a result of demethylation of its upstream promoter. Overexpression of CUL5 mRNA and protein in Ishikawa H endometrial cancer cells resulted in decreased cell proliferation and in a reduction in CUL5-RING E3 ligase downstream clients JAK2 and FAS-L. In the present study, we found that CUL5 expression was significantly decreased in both endometrioid and serous endometrial adenocarcinomas with the more aggressive serous type displaying a higher reduction (-4.3-fold) than the less aggressive endometrioid type (-2.9-fold). Altered expression of cullin-5 (CUL5), a member of the cullin-RING E3 ubiquitin ligase family, has been implicated in a number of types of cancers including breast, cervical and hepatocellular cancers.

Protein scaffold protein client