NRBP represents a new family of evolutionarily conserved proteins with homology in C. elegans, black nematodes, mice and humans. Overexpression of NRBP in COS-1 cells fails to activate possible downstream targets of Rac3, including the JNK pathway, p38 pathway, or actin cytoskeleton rearrangement. In addition, NRBP failed to co-localize with actin-based stress fibers or microprojections or subcortical actin. However, overexpression of NRBP caused large number of Golgi-related markers p58 to be redistributed to more peripheral locations in the cell, which is consistent with the damage of endoplasmic reticulum transport to Golgi. Immunocytochemistry showed that NRBP and activated Rac3 are co-localized in the endometrium and in the periphery of the cells in lamellipodia. These results indicate that NRBP plays a role in subcellular transport and may be targeted to specific subcellular locations by interacting with small GTPases of the Rho family.
Signal transduction pathways in cells are regulated by a variety of proteins. One type of adapter proteins plays a vital role in the regulation process. They can use specific domains and amino acid sequences/motifs to specifically regulate the binding between signal protein molecules or between signal proteins and lipid molecules, which play a role in connecting upstream and downstream signal transduction pathways. It plays an important role in connection and regulation. As a newly discovered protein, NRBP (nuclear receptor binding protein) is found in most normal human tissues, with the lowest expression in the thymus and the highest expression in the testis and placenta. NRBP has also been found in 15 human tumor cell lines including 293 cells and HeLa cells. The NRBP protein is composed of 535 amino acids. It is evolutionarily conserved and contains multiple functional domains. The N-terminal sequence rich in glutamic acid and serine may mediate the binding between NRBP and other SH2 domain-containing proteins. At the same time, it is speculated that NRBP may also be a nuclear receptor binding protein with two nuclear receptor binding domains, a nuclear localization signal (NLS: nuclear localization signal), and a nuclear export signal (NES). At present, there is not much research on the function of NRBP. It has been reported that it can bind to proteins such as Rac3, Mlf1, NS3, Jab1 and regulate related functions. Since there is no commercial anti-NRBP antibody, the NRBP fusion protein expressed in prokaryotic expression was prepared by genetic engineering method, and the specific polyclonal antibody of human NRBP was prepared and purified. In order to further study the function of the adaptor protein NRBP Laying the foundation.
Many human diseases, such as cancer and autoimmune diseases, are closely related to signal transduction pathways. The intracellular signal transduction system can regulate all processes of life activities, including cell proliferation, neural activity, development and differentiation, and metabolism. And muscle contraction. Linker proteins are involved in multiple signal pathways and are irreplaceable important proteins in the signal transduction process. Research on them will enable humans to understand more and more complex cellular signal pathways and provide necessary information for the development of drug targets related to signal pathways. The human NRBP gene is located on the 2p23 region of the chromosome, and the translocation of this band or adjacent bands is closely related to tumors and hematopoietic disorders. In 2002, De Langhe and other scientists discovered that NRBP binds to Rac3 of the Rho family, and over-expressed NRBP can block the transmission of the Golgi marker protein p58 from the endoplasmic reticulum to the Golgi. The homology of the amino acid sequence of murine MADM and human NRBP is as high as 98%. It has been found that it can interact with myeloid leukemia factor Mlf1, recruits serine kinase to phosphorylate Mlf1, and initiates the binding of Mlf1 to the important protein 14 -3 -3ζ, M1 phase MADM overexpressed in monocytes can regulate cytokine-induced cell differentiation by regulating the cell distribution of Mlf1. At the same time, our previous research found that NRBP may play an important negative regulatory role downstream of the TCR pathway through the transcriptional activator Jab1. Overexpression of NRBP can significantly inhibit the activity of TCR or PMA-induced transcription factors NFAT and AP-1 in Jurkat T cells.