Phosphorylated YBX2 is Stabilized to Promote Glycolysis in Brown Adipocytes
51 Pages Posted: 11 Jan 2022 Publication Status: Review Complete
More...Abstract
Y-box binding protein 2 (YBX2) is an essential modulator of brown adipose tissue (BAT) activation, yet the regulation on its own expression and involved mechanism remains unclear. Herein, we found YBX2 protein level, but not mRNA level, was induced upon acute β-adrenergic signaling, which indicates YBX2 can be YBX2 post-transcriptionally modulated. YBX2 was a dual substrate for both AMPK and Akt2. The phosphorylation at Thr115 by AMPK or at Ser137 by Akt2 facilitated YBX2 accumulating in brown adipocytes by decreasing ubiquitination-mediated degradation. Loss of Ybx2 in brown adipocytes in vivo and in vitro reduced the expression of glycolytic enzymes and lactate production. Conversely, overexpression of Ybx2 robustly promoted glycolysis. Mechanistically, YBX2 modulated translation of glycolytic genes via direct binding to 5’-UTR of these genes. Taken together, these findings suggest YBX2 is rapidly responsive to thermogenic stimuli by phosphorylation modification, and stabilized YBX2 helps to boost glycolysis in brown adipocytes.
Keywords: Brown adipocytes, YBX2, AMPK, Akt, Glycolysis
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