Immunoproteasome enhances intracellular proteolysis of myelin basic proteinстатья

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Дата последнего поиска статьи во внешних источниках: 16 сентября 2020 г.

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[1] Immunoproteasome enhances intracellular proteolysis of myelin basic protein / E. Kuzina, E. Chernolovskaya, A. Kudriaeva et al. // Doklady Biochemistry and Biophysics. — 2013. — Vol. 453, no. 1. — P. 300–303. Proteasome is a multisubunit protein complex that exhibits proteolytic activity and is present in the nuclei and cytoplasm of cells. The 20S proteasome, which has a molecular weight of 700 kDa and a sedimentation coefficient of 20S, is present as a proteolytic core in a more complex particle, the 26S proteasome. The degradation of proteins in the cell is regulated by the ubiquitinylation system, which marks the old or defective protein molecules for their recognition by the proteasome and subsequent proteolysis. One of the key biological functions of the proteasome is the hydrolysis of intracellular proteins to the antigenic peptides, which are then presented on the cell surface on the major histocompatibility complex class I molecules. Recent studies indicate the existence of a molecular mechanism by which the peptides generated by the proteasome can also be presented on the major histocompatibility complex class II molecules. The catalytic activity of a constitutive proteasome is mediated by three subunits, β1, β2, and β5, which are constitutively expressed in cells. The proteasome, which contains corresponding immunosubunits β1i, β2i, and β5i the catalytic center, is called the immunoproteasome and is significantly different from the constitutive proteasome in its activity and substrate specificity. The set of antigenic peptides produced by the immunoproteasome differs from the set of peptides produced by the constitutive proteasome. It was recently shown that immunoproteasome not only changes the degradation spectrum of antigenic proteins but also ensures the maintenance of protein homeostasis under conditions of oxidative stress caused by the action of interferons on the cell. The amount of immunoproteasome in cells increases in various diseases (hematologic malignancies, rheumatoid arthritis, autoimmune colitis, Alzheimer’s disease, and Huntington disease). One of the most common and socially significant autoimmune diseases is multiple sclerosis (MS), which is characterized by the destruction of the myelin sheath of nerve fibers. Myelin basic protein (MBP) is a major autoantigen in multiple sclerosis. At present, the molecular mechanisms underlying the development of multiple sclerosis are being actively studied. Recent studies have demonstrated an important role of both the constitutive proteasome and the immunoproteasome in the development of this disease. Earlier, we studied in vitro the proteolysis of MBP by the proteasome isolated from normal mice and mice with experimental autoimmune encephalomyelitis (EAE), an experimental model of MS. During further development of this research, we created a model to study the intracellular proteolysis of MBP in mammalian cells. Here we show that the intracellular hydrolysis of MBP is significantly accelerated when the proteasome–immunoproteasome balance is shifted toward the latter. [ DOI ]

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