S100A11 Is A Novel Player In Cholesterol Biosynthesis

Cholesterol plays an important role in the body.It can not only regulate the stability of cell membranes,but also is the precursor of many important substances in the body.Cholesterol needs to be maintained in a steady state.Once cholesterol metabolism is imbalanced,it will cause a series of pathological and physiological changes.This study found that calcium-binding protein S100A11 may be involved in the regulation of cholesterol metabolism from the non-alcoholic fatty liver disease model of tree shrews.Through a series of experiments,we found that S100A11 can respond to cholesterol and increase liver cholesterol content.Further research found that S100A11 up-regulates cholesterol in the liver through the classic cholesterol synthesis pathway.SREBP2 is usually regulated by INSIG and SCAP proteins to mature.We found that S100A11 does not regulate INSIG and SCAP,but matures SREBP2 through importin?.However,we found that S100A11 does not directly interact with importin?,so there are other intermediate molecules to regulate importin?.Through mass spectrometry,co-immunoprecipitation and combined with existing research reports,we found that S100A11 can bind to Annexin A1.Further studies have found that ANXA1 can bind to the importin-SREBP2 complex in the liver.These results suggest that S100A11 is Connecting importin? through ANXA1 leads to the entry of SREBP2 into the nucleus.In summary,we found that the calcium binding protein S100A11 can regulate the classic SREBP2 pathway,leading to increased liver cholesterol synthesis.This provides a new perspective and theoretical basis for revealing the molecular mechanism of cholesterol metabolism regulation and perfecting the cholesterol metabolism regulation network.