BAG5 protein can save the function of anti-oncoprotein p53

According to research using recombinant dog proteins, among the anti-oncoproteins found so far, p53 is undoubtedly one of the most well-known. It can achieve the curative effect of cancer by affecting cell division, apoptosis, metabolism and other important processes. In nearly half of the tumors, the gene TP53 which expresses this transcription factor show mutations, making p53 lose anti-cancer function. And some functional (GOF) mutations may even make p53 directly "renegade" and promote canceration and tumor resistance.

Mutant p53 is characterized by a greater stability, reflected by being more difficult to be mediated and degradated by ubiquitin ligase MDM2 and CHIP. Interestingly, this stability is limited to cancer cells but not in the normal cells. This allows the mutant p53 to accumulate in the tumor to a high level so as to play its role in promoting cancer. Then, what kind of difference do cancer cells have to make mutant p53 to accumulate at a high level?

Recently, the research team of Prof. Wenwei Hu and Prof. Zhaohui Feng of Rutgers, The State University of New Jersey found that BAG-2-related anti-apoptotic gene (BAG) family proteins BAG5 and BAG2 can prevent pan- Ligase and mutant p53 binding, thereby giving the latter cell-specific stability in the cancer. The results are published in the recent Nature Publishing Group publication Cell Discovery.

In a variety of human breast cancer and lung cancer cell lines and other systems, BAG5 of the five BAG domain can be R175H, R248W or R273H mutant p53 DNA binding domain (DBD) interaction, and BAG5 and wild type P53 between no affinity. At the same time, BAG2, another member of the BAG family, was found to have synergistic effects with BAG5 in enhancing mutant p53 stability. Concomitantly, when BAG5 was overexpressed, the level of mutant p53 was increased in cancer cells, and it decreased when BAG5 was knocked down.

By this interaction, BAG5 prevents MDM2 and CHIP from modifying ubiquitination of mutant p53, thereby ultimately inhibiting degradation of the p53 by the proteasome. Further experiments have shown that BAG5 is essential for the development of functional R248W mutations to play a role in carcinogenesis, including the ability to promote proliferation, proliferation, and drug resistance in cancer cells. It is worth noting that BAG5 is overexpressed in a variety of tumors including breast cancer, skin cancer, colorectal cancer, lung cancer and so on. And the higher the expression level, the worse the prognosis of patients.

BAG family proteins play an important regulatory role in cell division, differentiation and apoptosis, and their common BAG domains have molecular chaperone activity. In this study, BAG5 was found to have proto-oncogenic properties that enhance the ability of cancer cells to proliferate, diffuse and resist drug resistance by increasing the level of functional mutant p53 protein. Therefore, BAG5 has a potential as a therapeutic target for tumors expressing the aforementioned p53 protein. Flarebio provides good-quality recombinant proteins such as recombinant CDH2.