Molecular regulation and biological function of NRF3 (NFE2L3) in cancer cells

• Main Author: A M Masudul Azad Chowdhury
• Format: Others
• Language: en
• Published: 2017
• Online Access: https://doshisha.repo.nii.ac.jp/?action=repository_uri&item_id=1390; http://id.nii.ac.jp/1707/00001382/; https://doshisha.repo.nii.ac.jp/?action=repository_action_common_download&item_id=1390&item_no=1&attribute_id=21&file_no=1; https://doshisha.repo.nii.ac.jp/?action=repository_action_common_download&item_id=1390&item_no=1&attribute_id=21&file_no=2

I found multiple regulation of NRF3 activities promotes cell proliferation. My analyses reveal (1) under physiological conditions, NRF3 is rapidly degraded by the ER-associated degradation (ERAD) ubiquitin ligase HRD1 and valosin-containing protein (VCP) in the cytoplasm; (2) NRF3 is also degraded by β-TRCP, an adaptor for the Skp1-Cul1-F-box protein (SCF) ubiquitin ligase in the nucleus; (3) NRF3 mediates gene expression of the cell cycle regulator U2AF homology motif kinase 1 (UHMK1) for cell proliferation; (4) the nature of the activation mechanism of NRF3 is not the inhibition of its HRD1-VCP-mediated degradation. Collectively, this study provides us many insights into biological function of NRF3 in cancer cells. === 博士(理学) === Doctor of Philosophy in Science === 同志社大学 === Doshisha University