UXT Is a LOX-PP Interacting Protein That Modulates Estrogen Receptor Alpha Activity in Breast Cancer Cells

The lysyl oxidase proenzyme propeptide region (LOX-PP) is a tumor suppressor protein whose mechanism of action is not completely understood. Here, the Ubiquitously expressed Transcript (UXT) was identified in a yeast two-hybrid assay with LOX-PP as bait and confirmed as a novel LOX-PP associating protein. UXT, a prefoldin-like protein, is ubiquitous in human and mouse. Since UXT modulates androgen receptor transcriptional activity in prostate cancer, we studied its role in breast cancer. Breast tumors and derived cell lines overexpressed UXT. UXT was able to associate with the estrogen receptor alpha (ER) and decrease its transcriptional activity and target gene expression. Conversely, UXT knockdown increased ER element-dependent transcriptional activity. Ectopic LOX-PP relocalized UXT to the cytoplasm and decreased its stability. UXT ubiquitination and depletion in the presence of LOX-PP was rescued by a proteasomal inhibitor. In summary, proteasome-mediated turnover of UXT upon interaction with LOX-PP releases repression of ER transcriptional activity. J. Cell. Biochem. 118: 2347-2356, 2017. © 2017 Wiley Periodicals, Inc.