Crosstalk Between Acetylation and Ubiquitination Contributes to PRMT1 methyltransferase Homeostasis

Understanding its regulation is crucial for therapeutic targeting. We demonstrate that p300-mediated acetylation of PRMT1 at K228 triggers degradation via FBXL17-dependent ubiquitination at K145.

Using mass spectrometry, cellular biochemistry, and genetic code-expansion, we reveal the crosstalk between acetylation and ubiquitination in PRMT1 homeostasis, highlighting mechanisms governing protein stability. This study results in Identification of K228 acetylation and K145 ubiquitination sites on PRMT1, FBXL17 as the E3 ligase mediating PRMT1 ubiquitination and interdependence of p300 acetylation and FBXL17 ubiquitination in PRMT1 degradation.