Regy Regulate The Molecular Mechanism Of DEN Induced Liver Cancer

REG gamma also know as PA28 gamma, PSME3 or Ki antigen, belong to REG or lls family of proteasome activator which has been shown to bind and activate 20S proteasomes. REGgamma can activates the ubiquitin-independent degradation of SRC-3, the same time it also can promote the regulation of several important protein degradation, such as p21.REG gamma has been reported to overexpressed in several cancer, including liver cancer.Hepatocellular carcinoma (HCC) is a worldwide common cancer, accounting for about 90% of all liver tumor, is the third cancer death reason. There are many factors that can induce HCC many, including HCV, HBV infection, consumption of aflatoxin contaminated food, long-term excessive alcohol intake, and exposure to chemical carcinogens, etc. HCC general will go through the following steps:fat, liver fibrosis, liver cirrhosis, hepatocellular carcinoma, but the above process does not necessarily occur in one patients, its need combine with the pathology background.Chkl is cell cycle checkpoint kinases, play an important role in DNA damage response repair and cell cycle checkpoint to ensure genome integrity and correctness. DNA damage induce ATR activation, then phosphorylate CHK1 at S317 and S345 sites, phosphorylated CHK1 enter into activated state. on the one hand, the activation of CHK1 phosphorylation CDC25A and CDC25B/C, make it loss CDK combining ability, and the cell cycle stop at the G1/S and G2/ M point, on the other hand CHK1 collect DNA damage repair proteins such as FANCE, RAD51 into the damage sites, make sure the replication is correct. In addition, the CHK1 role in tumorigenesis was controversial, as proto-oncogene mainly because CHK1 can inhibit apoptosis, increase the radiation and chemotherapy tolerance; but as a tumor suppressor gene mainly due to CHK1 repair DNA damage to prevent genetic mutations, but specific mechanism is not clear at present.Now have papers report that REG gamma was involved in the process of DDR, but specific regulatory mechanism is not clear.And from our existing data found that REG gamma can reulate CHK1/2 in protein level, cause DDR process restrained, and then accumulation of DNA damage and finally induce cancer. Therefore, study the REG gamma function in the HCC development is meaningful.