UHRF1 Negatively Regulates Ampk Activity By Promoting AMPK Dephosphorylation

AS a nucleus multifunctional protein,UHRF1 has been characterized for its role in DNA methylation,DNA damage repair,cell cycle progression and embryonic development.However,little is known whether UHRF1 is involved in metabolic regulation.AMPK is well-known for its central role in metabolic regulation.AMPK is activated by nutrition deprivation.Once activated,in one hand,AMPK can promote glucose metabolism,fatty acid ? oxidation and autophagy.In the other hand,it can inhibit protein synthesis,lipid synthesis,gluconeogenesis and glycogen storage.We found that UHRF1 negatively regulates AMPK activity in HEK293 T cells by promoting AMPK dephosphorylation.Overexpression or knockdown of UHRF1 can promote or reduce the interaction between AMPK and phosphatase PP2 A.We also found that in HEK293 T cells,UHRF1 can regulate HIF-1? protein levels,glycolytic gene transcription,and lipid metabolism by regulating AMPK.In tumor cells,it is reported that AMPK reduces the Warburg effect and inhibits cell growth.Meanwhile UHRF1 is highly expressed in tumor cells.Combining our results,we speculate that UHRF1 may promote tumor cell growth and glycolysis though suppressing AMPK activity.Our research provides evidence and mechanism by UHRF1 regulates cellular metabolism by its ability to inhibit AMPK activity.