Biochemical and Biophysical Research Communications, Vol.534, 347-352, 2021
AMP-activated protein kinase regulates beta-catenin protein synthesis by phosphorylating serine/arginine-rich splicing factor 9
beta-catenin is a multi-functional protein with a central role in regulating embryonic development and tissue homeostasis. The abnormal accumulation of beta-catenin, due to disrupted beta-catenin degradation or unregulated beta-catenin synthesis, causes the development of cancer. A recent study showed that the overexpression of proto-oncogene serine/arginine-rich splicing factor 9 (SRSF9) promotes beta-catenin accumulation via binding beta-catenin mRNA and enhancing its translation in a manner that is dependent on the mechanistic target of rapamycin (mTOR). However, the regulation of the interaction between SRSF9 and mRNA of beta-catenin remains unclear. Here, we show that AMP-activated protein kinase (AMPK) phosphorylates SRSF9 at the RNA-interacting SWQDLKD motif that plays a major role in determining substrate specificity. The phosphorylation by AMPK inhibits the binding of SRSF9 to beta-catenin mRNA and suppresses beta-catenin protein synthesis caused by SRSF9 overexpression without changing the beta-catenin mRNA levels. Our findings suggest that AMPK activators are potential therapeutic targets for SRSF9-derived overproduction of beta-catenin in cancer cells. (C) 2020 Elsevier Inc. All rights reserved.