|Huang Gang and his team from shanghai institute of health released new achievements in Scientific Reports and published online|
Recently, the international academic journal Scientific Reports published online the latest research results of Huang Gang and his group of “Interaction with Pyruvate Kinase M2 Destabilizes Tristetraprolin by Proteasome Degradation and Regulates Cell effort in Breast Cancer”. The study reveals the Pyruvate Kinase M2 (PKM2) as a hot research to promote Cancer gene that can degrade Tristetraprolin suppressor gene (TTP) of post-translational modifications and promote TTP into the Proteasome Degradation pathways, and it ultimately affects the Breast Cancer Cell Proliferation.
Recently, the deepening of research on tumor and tumor cell sugar metabolic abnormalities was again taken seriously, and the fact that sugar metabolism is found to be closely related to pyruvate kinase M2 type (PKM2) also becomes a hot research. The expression of PKM2 in many tumor cells such as liver cancer, pancreatic cancer, lung cancer, and adenocarcinoma in the cancer is comparatively high. The PKM2 is the speed limit in the process of glycolytic enzyme, at the same time it is also significant in the process of oxidative phosphorylation to glycolysis so that it plays an important role, and the extent of malignant tumor, is closely related to the tumor metastasis and tumor development, etc. The expression level in vitro and in vivo experiments of PKM2 can significantly enhance the anaerobic glycolysis effect of tumor, and promote the rapid growth of the tumor, which in turn after knockout PKM2 can reduce anwar‘s effect, and inhibit tumor growth. At present, PKM2 research, is mainly divided into the following three categories: one is based on the antitumor mechanism research, the other is based on the PKM2 high-through put random screening of PKM2 and substrate based combination of transition state drug design. The use of some antibody molecules and small molecular peptides can combine PKM2 proteins, thereby inhibiting PKM2 catalytic activity, and interference off PKM2 can obviously increase after some effective chemotherapy effect, and improvement in the tumor chemotherapy sensitivity, is expected to be used in clinical.
Huang jing qian and other PHD researchers in Huang Gang’s research team are under the guidance and leadership of professor huang gang in this research. Their study found that PKM2 can combine with TTP protein levels, which promote the phosphorylation of TTP, to cause its ubiquitin level, eventually lysosome degradation by TTP. TTP degradation and promote oncogene mRNA level also reduced accordingly. At the same time, the udder cell proliferation ability have also been significant regulation. While using p38 lightning inhibitor SB203580 or p38 lightning small interference RNA, the degradation caused by PKM2 TTP will be significantly diminished, speculated that p38 lightning/MAPK pathway may be involved.
The high expression in PKM2 exists in most tumor and plays an important role in the development of tumor. The research reveals the PKM2 by combined with TTP to promote its molecular mechanism of protein degradation, as a potential tumor therapeutic target for the PKM2 lay a molecular basis.
This work is supported by the national natural science foundation of China, major national drug discovery, the state ministry of science and technology and other major fundings as well.
The online address of the link for this article : http://www.nature.com/articles/srep22449