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ERRalpha protein is stabilized by LSD1 in a demethylation-independent manner.
PLoS One, 12(11):e0188871.
The LSD1 histone demethylase is highly expressed in breast tumors where it constitutes a factor of poor prognosis and promotes traits of cancer aggressiveness such as cell invasiveness. Recent work has shown that the Estrogen-Related Receptor alpha (ERRalpha) induces LSD1 to demethylate the Lys 9of histone H3. This results in the transcriptional activation of a number of common target genes, several of which being involved in cellular invasion. High expression of ERRalpha protein is also a factor of poor prognosis in breast tumors. Here we show that, independently of its demethylase activities, LSD1 protects ERRalpha from ubiquitination, resulting in overexpression of the latterprotein. Our data also suggests that the elevation of LSD1 mRNA and protein in breast cancer (as compared to normal tissue) may be a key event to increase ERRalpha protein, independently of its corresponding mRNA.
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