REGγ Is Linked To TGFβ,p53 And Its Downstream Genes

REGy, also known as 11S proteasome activator, plays an important role in cell cycle regulation through the degradation of p21(CDKI) mediated by REGy, and that it is concerned with the tumorigenesis through the degradation of p53. TGF(3, that is, transforming growth factor beta, can inhibit the cell growth through the up regulation of p15 and p21.It is also involved in cell cycle regulation. p53, as a most important factor of the tumorigenesis, exerts its function together with its downstream genes. Obviously, they are all important regulators of the cell cycle. Up to now, there is no report about the relation between REGγand TGFβ, REGy and P53 downstream genes.In the research of the REGγand TGFβ,we found that the expression of REGy can be inhibited by TGF(3, and that REGy has relation with the p21 and p15,which are downstream genes of TGFβ. All these data reveal that the cell growth induced by TGF(3 is regulated by REGy. The high expression of p21 and p15 are involved in the REGy inhibition. This study demonstrates that REGγhas some relation with TGFβ.As one of the most important tumor suppressor genes, p53 is combined with its downstream genes to play an important role in the tumorigenesis. Through the meta-analysis of the publicly microarray database, we find some genes whose expression has some relation with REGy in four tumor tissues, including colon, thyroid, liver and lung. There are three kinds of genes:p53 downstream genes, myc genes and some others.We focused our attention on the p53 downstream genes and find that 29 of the p53 downstream gene are related with REGy. That is,80% of the p53 downstream genes are consistent with the computer analysis. Some of the attention-attracting genes, such as BAX, PTEN, GADD45, CDK2, are related with REGy expression. Some of these genes have the tumor specificity, and some are affected by p53 activation. This study demonstrates that REGγhave some relation with the p53 downstream genes. Maybe there are some interaction between them, which provide a new idea for the exploration of the new REGγtarget genes.REGγcan degrade p53 by enhancing the MDM2 mediated ubiquitination. But we have no idea about the direct interation between REGγand p53. We have proved that they can interact with each other, and the binding site is the 100-290AA subunit of p53.This new result has provided us that REGγmay degrade the p53 directly, except the MDM2 mediated method. But the specific binding site need our further study.In this project, we discuss the relation of REGγand TGFβ, p53 and its dowmstream genes. We get the results that TGFβinduced cell growth is regulated by REGγ,80% of the computer analysis p53 genes are related with REGy expression, and that REGy can interact with p53 directly. These new findings help us to explore the unknown biological function of REGy and pave the way for revealing new mechanism of TGFβsignaling path way and tumorigenesis.