AMP-activated protein kinase regulates β-catenin protein synthesis by phosphorylating serine/arginine-rich splicing factor 9

• Published in: Biochemical and biophysical research communications 2021-01, Vol.534, p.347-352
• Main Authors: Matsumoto, Eri, Matsumoto, Yu, Inoue, Jun, Yamamoto, Yuji, Suzuki, Tsukasa
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Amino Acid Sequence; AMP-Activated Protein Kinases - metabolism; AMPK; beta Catenin - biosynthesis; beta Catenin - genetics; Binding Sites; HEK293 Cells; Humans; In Vitro Techniques; Mechanistic Target of Rapamycin Complex 1 - metabolism; mTORC1; Mutagenesis, Site-Directed; Phosphorylation; Protein Binding; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Serine-Arginine Splicing Factors - chemistry; Serine-Arginine Splicing Factors - genetics; Serine-Arginine Splicing Factors - metabolism; SRSF9; Substrate Specificity; β-catenin
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.11.079

β-catenin is a multi-functional protein with a central role in regulating embryonic development and tissue homeostasis. The abnormal accumulation of β-catenin, due to disrupted β-catenin degradation or unregulated β-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 β-catenin accumulation via binding β-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 β-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 β-catenin mRNA and suppresses β-catenin protein synthesis caused by SRSF9 overexpression without changing the β-catenin mRNA levels. Our findings suggest that AMPK activators are potential therapeutic targets for SRSF9-derived overproduction of β-catenin in cancer cells. •SRSF9 is a novel substrate of AMPK.•The phosphorylation of the SWQDLKD motif of SRSF9 inhibits its binding to β-catenin mRNA.•AMPK suppresses SRSF9-induced β-catenin protein production.