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Regulation Of SirT1 Activity By Ribosomal Protein L13

Posted on:2014-05-12Degree:MasterType:Thesis
Country:ChinaCandidate:Y ZhengFull Text:PDF
GTID:2180330482983382Subject:Biomedicine
Abstract/Summary:PDF Full Text Request
The silent information regulator 2 (Sir2) is a NAD-dependent protein deacetylase that obviously extends lifespan in yeast. Sirtuins.Mammalian orthology of yeast sir2,have seven proteins of the sirtuin family (SirT1-7) that share the same catalytic domain with Sir2.They comprises 275 amino acids highly conserved catalytic core domain. SirT1 is the first found and best understood among the seven members of the sirtuin family.As a deacetylase, SirT1 is connected with crucial stress-responsive signal transduction pathways. It can also regulate the activity of several other key cellular proteins,which have emerged as critical regulators of metabolism, longevity, cell survival.cell growth.differentiation, senescence.apoptosis, cancer and so onThe ribosome is a large protein synthesis factory, which can be found in all living cells.Ribosomes consist of two major subunits—he small ribosomal subunit reads the mRNA, while the large subunit joins amino acids to form a polypeptide chain.Ribosomal proteins are major components of ribosomes,and constitute ribosomes with ribosomal RNA in oder to finish protein synthesis.Recent data have show them to have extra functions.Mammal ribosome consist of a small 40S subunit and a large 60S subunit,60S ribosomal protein L13 is a protein that is encoded by the RPL13 gene,is the component of 60S subunit. It belongs to the L13E family of ribosomal proteins,it also called the breast basic conserved protein 1(BBC1).In this study, we innovatively found that L13 is a new binding protein with SirT1, They have the same location in vivo,and is the protein level of SirT1 that can be downregulated by L13 but not the mRNA level.We have proved that L13 can promote ubiquitination of SirT1. L13 can also associate with some deubiquitinating enzymes,such us usp2a,usp2b,uchl1,uchl2.Co-tansfeced with these deubiquitinating enzymes can decrease ubiquitination of SirT1 by L13. In addition,we also found that ribosomal stress can enhance the binding of SirT1 and L13. Our work still have a great deal of imperfection.it needs to be improved.
Keywords/Search Tags:ribosomal protein L13, SirT1, ubiquitination, ribosomal stress
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