FBXL10 promotes ERR? protein stability and proliferation of breast cancer cells by enhancing the mono-ubiquitylation of ERR?.

The underlying mechanism of orphan nuclear receptor estrogen-related receptor ? (ERR?) in breast cancer was investigated by identifying its interaction partners using mass spectrometry. F-box and leucine-rich repeat protein 10 (FBXL10), which modulates various physiological processes, may interact with ERR? in breast cancer. Here, we investigated the interaction between FBXL10 ...
and ERR?, and their protein expression and correlation in breast cancer. Mechanical studies revealed that FBXL10 stabilized ERR? protein levels by reducing its poly-ubiquitylation and promoting its mono-ubiquitylation. The reporter gene assay and examination of ERR? target genes validated the increased transcriptional activity of ERR? due to its increased protein levels by FBXL10. FBXL10 also increased ERR? enrichment at the promoter region of its target genes. Functionally, FBXL10 facilitated the ERR?/peroxisome proliferator-activated receptor gamma coactivator 1 ? (PGC1?)-mediated proliferation and tumorigenesis of breast cancer cells in vitro and in vivo. Our results uncovered a molecular mechanism linking the mono-ubiquitylation and protein stability of ERR? to functional interaction with FBXL10. Moreover, a novel regulatory axis of FBXL10 and ERR? regulating the proliferation and tumorigenesis of breast cancer cells was established.
Mesh Terms:
Animals, Breast Neoplasms, Cell Line, Tumor, Cell Proliferation, F-Box Proteins, Female, Gene Expression Regulation, Neoplastic, HEK293 Cells, HeLa Cells, Humans, Jumonji Domain-Containing Histone Demethylases, MCF-7 Cells, Mass Spectrometry, Mice, Neoplasm Transplantation, Promoter Regions, Genetic, Protein Stability, RNA-Binding Proteins, Receptors, Estrogen, Ubiquitination
Cancer Lett
Date: Dec. 01, 2020
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