The Study Of Histone Deacetylase SirT7

Sirtuins are NAD+-dependent protein deacetylases that connect metabolism and cellular homeostasis.SirT7 is the only sirtuin localized in nucleoli.SirT7 is an important regulator of rDNA transcription via its association with RNA Pol I.The rDNA transcription is the initiation of whole cell life.It is a critical limit process in the balance of the cellular energy and homeostasis.So it will be interesting to research the activity of SirT7.The phosphorylation of SirT7 was reported to be regulated by CDK1-cyclin B,but there is no other data concerning the regulation of SirT7.REGy,one of the 11S proteasomal activators,localizes in nucleoplasm.REGy binds to the 20S proteasome and mainly promotes ATP-and ubiquitin-independent protein degradation.REG? involves in various biological processes by degrading different proteins.For instance,REG? has been implicated in the regulation of cell progress via P21.And REG? enhances MDM2-mediated p53 degradation,inhibits apoptosis.In addition,REGy proteasome can also regulate hepatic lipid metabolism through inhibition of autophagy.Our studies focus on the regulation of REGy-SirT7-rDNA transcription.We found that REG? physically binds to SirT7.REGy overexpression leads to SirT7 nucleoplasmic redistribution.The association of REG? and SirT7 negatively regulates rDNA transcription.There are two implications in our findings:first,we found an upstream regulator of SirT7;second,we revealed the close contact between proteasome system and ribosome.Furthermore,we made a study on the phosphorylation of SirT7 and identified a phosphorylation site of SirT7 by a phospho-specific antibody,which established a theoretical basis for our further study of phosphorylated SirT7 involving in rDNA transcription.