动物实验,类泛素化E3连接酶 z-bo 2020-08-19 588

　　Recently, American scientists published new research progress online in the international academic journal "Cell Death and Differentiation". They found that the E3 ligase RCAD/Ufl1 of the ufm1 connection system plays an important role in regulating the function of mouse hematopoietic stem cells and hematopoietic development.

　　Ufm1 (ubiquitin-foldmodifier1) connection system is a new type of ubiquitin-like modification system whose biochemical properties are similar to other ubiquitin-like modification systems. The Ufm1 pathway catalyzes the modification of target protein pairs through three specific enzymes E1 (uba5), E2 (ufc1) and E3, but there are few studies on E3 ligase.

　　CAD/Ufl1 has the function of ufm1E3 ligase, which can mediate the ubiquitination modification (ufmylation) of DDRGK1 and ASC1. RCAD/Ufl1 is the protein response (UPR) in the estrogen receptor pathway) It plays an important role in the process of denaturation .

　　In this study, the researchers found that in addition to the above-mentioned functions, RCAD/Ufl1 also plays an important role in embryonic development, hematopoietic stem cell survival, and erythroid differentiation. Researchers found that removing RCAD/Ufl1 in germ cells and somatic cells would disrupt the development of hematopoietic function, leading to severe anemia, loss of blood cells, and ultimately death of animals. At the same time, the removal of RCAD/Ufl1 causes the endoplasmic reticulum stress to cause an unfolded protein response (UPR) in bone marrow cells. In addition, the loss of RCAD/Ufl1 can prevent the degradation process through autophagy, increase mitochondrial content and ROS accumulation, cause DNA damage, activate p53 and promote hematopoietic stem cell death.

　　Generally speaking, this study provides the first genetic evidence that RCAD/Ufl1 plays an important role in the hematopoietic development of mice, and RCAD/Ufl1 is a key regulatory factor in the cellular stress response and immune process. It has been shown to be important for regulation in homeostasis, and to form a new protein regulatory network is very important.