CUL5 Is Involved in Proteasome-Degradation of BiP in Breast Cancer Cells

Abstract

The E3 ubiquitin ligase Cullin 5 (CUL5) has been linked to a variety of cell biological functions, such as developmental process regulation, DNA repair, and cell cycle control, but the role of CUL5 in the unfolded protein response (UPR) remains unclear. We found that the knocked-down of the CUL5 gene results in the upregulated levels of binding immunoglobulin protein (BiP) protein, a major chaperone protein in unfolded protein response (UPR), whereas the over-expression of CUL5 downregulated BiP protein levels in breast cancer cells. Further investigation revealed that CUL5 binds with BiP, leading to the ubiquitination of BiP. Our findings suggest that CUL5 is involved critically in the proteasome-degradation of BiP, leading to weaker UPR.