The Impact Of REGγ On Ageing And Liver Cancer Progression

The ubiquitin protein degradation pathway is the core in protein degradation. It regulates the cell cycle, DNA replication, transcription, signal transduction, apoptosis, and other important life activities. As a newly discovered proteasome pathway, the REG gamma (a proteasome activator) proteasome could degrade proteins through ubiquitin- and ATP-independent manner. A series of substrates of REG gamma has been found, such as SRC3, p21, HCV core protein, PKA, and SirTl, all bearing important functions. But how REG gamma plays a role in vivo remains not very clear. Based on ours study in animal, we found that REG gamma knockout (KO) mice are more prone to develop premature aging than wild type mice. Moreover, during the period of observation, we also found that about 10% of wild type mice died because of the different kinds of tumors; On the contrary, the tumor was not be found in knock out mice though KO mice died even earlier. These results suggested that REG gamma might have a correlation with augmented incidence of tumor. Therefore, we focused on carcinogen induced progression of liver cancers in REG gamma wild type mice and KO mice. After injection of DEN, REG gamma wild type mice are more vulnerable to develop liver cancer and have higher sensitivity to DEN stimulation. These studies provide further evidence for proteasome mediated regulation of ageing processes and liver carinogenesis.