Gankyrin is a recently discovered oncoprotein that is a component of the 19S regulatory cap of the proteasome. It contains a 33-amino acid ankyrin repeat that forms a series of alpha helices. It plays a key role in regulating the cell cycle via protein-protein interactions with the cyclin-dependent kinase CDK4. After searching for the gene pool, the researchers found that the gene sequence of gankyrin was exactly the same with that of p28 (Nas6p) which was found in 1998 by Hori et al. Then it was named as p28GANK. Cancer gene p28GANK coded protein is a non-ATP complex enzyme that human 26S proteasome (26S Proteasome) regulating subunit 19S/PA700 complex, the nucleic acid sequence of which contained five units-arranged in series ANK repeated units, and its conserved ankyrin sequences mediate protein-protein interactions.
20S protein corpuscle in 26S proteasome is a place at which to degrade certain misfolded proteins or cell cycle proteins in vivo. It is not clear about the specific molecular mechanisms of oncoprotein P28GANK in 26S proteasome protein degradation process. Previous studies found that cancer protein P28-GANK regulates the degree of phosphorylation of Rb through direct interaction with Rb. In addition, after the binding of P28GANK and pRb, they may also promote pRb degradation through S6bATP enzymes of 26S proteasome; or pRb directly combines with the 20S nucleus of 26S proteasome to mediate its own degradation.
Through a variety of signaling pathways of P28GANK above regulation CDK4 / CyclinD1 / p16INK4a / Rb1 / E2F-1, researchers knew that the signal transduction pathway had a very important role in the development of HCC. Therefore, interventions against the pathway and related targets may be a new way of treatment of liver cancer. This study mainly focused on critical areas and amino acids of the interaction between P28GANK and Rb in the signal transduction pathway of CDK4 / CyclinD1 / p16INK4a / Rb1 / E2F-1, using computer-aided drug design program to design specificity to block combined small molecule compound and conduct its biological function identification.
This is the first time to take Rb and spatial areas and key amino acid interactions as a target to use computer-aided drug design to conduct analysis of small molecule inhibitors on hepatocellular carcinoma p28GANK signal transduction mechanism. They have selected a specific biologically active small molecule compound, small molecules that can block the binding of Rb and P28GANK and inhibit the proliferation of liver cancer cells. Scientists also like to do experiments using recombinant rat protein and recombinant horse protein. It depends on what results you need.
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