Li Huimin: tumor suppressor protein drives cancer

Recently, scientists from the University of Pennsylvania and other places found that the growth of malignant tumors and the change of gene activity without change of DNA sequence are often directly related to the mutant p53 protein The relevant research results were published in the international famous journal Nature, which may provide help for the development of new strategies to deal with cancer that is difficult to treat TP53 is a frequently mutated gene of all human cancers, which can encode a tumor suppressor protein called p53 P53 usually suppresses tumors by regulating the cycle of cell division, and p53 protein also suppresses cancer by maintaining the rapid growth and division of cells When DNA is damaged, p53 will produce a series of protective effects to repair DNA damage If the damage is too serious, it will lead to cell death The mutation of TP53 gene will often destroy its normal function, and make the cell carrying damaged DNA continue to divide until cancer occurs In order to understand how mutant p53 function acquisition (GoF) plays a role, the researchers investigated the function of tumor derived cancer cell lines of patients carrying different types of p53 GOF instead of amino acids to see where these mutant forms of p53 will bind to the cancer cell genome Berger said, we found that the mutant p53 will bind and activate a series of genes including epigenetic characteristics, especially those related to histone methylation and acetylation; the p53 mutant protein of GOF will directly target the genes encoding epigenetic enzymes, including Mll1, mll2 and Moz Under normal circumstances, the epigenetic enzyme Mll1 will add methylation groups to histones to promote transcription and cell growth The researchers found that the mutant p53 protein will approach the Mll1 pathway, causing methylation changes of the whole genome histone, so that cell replication will not be controlled The change of epigenetic pathway often involves the occurrence of various types of cancer, which may provide a reasonable mechanism to help explain why the expression of uncontrolled cell replication occurs, and some research results show that p53 mutated by GOF can directly target the key epigenetic factors Now researchers can genetically inhibit Mll1 to inhibit cell proliferation, especially in tumors with p53 mutation Researchers can also test whether they can inhibit the function of Mll1 in pharmacology By using drugs targeting Mll1 activity, researchers also found similar inhibition effects on the growth rate of p53 mutant cells In this study, the researchers elucidated the new epigenetic mechanism hidden in the progression of GOF p53 mutation In this study, we found that some types of cancer may continue to develop with some special changes When these regulators are knocked out or pharmacologically inhibited, GOF p53 tumor cells can not arbitrarily replicate.