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Degradation of defective proteins
Proteasomes also degrade defective proteins that the cell failed to synthesize correctly (about 30% of all native proteins in the cell) and whose elimination takes place immediately during translation or shortly after it. If newly synthesized defective proteins are located in the endoplazmatickém retikulu (ER) – and here it is primarily a question of proteins misfolded into tertiary structures – they are subject to a process in which proteasomes cooperate with the ER and which is called ERAD (endoplasmic reticulum-associated degradation). During ERAD, the misfolded protein is first marked with a specific code (these are glycans), then it is transported across the ER membrane into the cytosol and degraded by adjacent proteasomes. In the case of non-native proteins that are poorly folded and aggregated, they are taken up in the cytosol using two compartments called JUNQ (juxta-nuclear quality control) and IPOD (insoluble protein deposit). Even these proteins are finally degraded in proteasomes. However, proteasomes do not only degrade defective proteins, but also significantly participate in the processing of functional proteins in the sense of influencing their function. Degradation of a protein can be an important part of various signaling events in the cell, as we will see below.

Nuclear and cytoplasmic proteasomes
Proteasomes are contained in the cytoplasm and in the nucleus, where they move freely and quickly. On the other hand, the transfer of proteasomes from the cytoplasm, where there are more of them, to the nucleus it cannot go in the other direction) is slow. During mitosis, the two separate populations of proteasomes, nuclear and cytoplasmic, can fuse and intermingle . The total amount of proteasomes in the cell is in the hundreds to thousands of nanograms per milligram of all cellular proteins, with the fact that it can be significantly greater in cancer cells than in healthy cells . Further details on the localization of proteasomes in the cytoplasm and nucleus can be found in the literature.

The ubiquitin-proteasome system
Degradation of proteins using proteasomes is a very sophisticated process that takes place within the framework of the so-called ubiquitin-proteasome system (UPS) or the so-called ubiquitin-proteasome pathway. An important role in this process is played by the small (76 amino acids, 8.5 kDa) protein ubiquitin, which was discovered as early as 1975 without its function being known. However, the name implies that this protein is abundant in all eukaryotic cells (it is "ubiquitous" i.e. "occurring everywhere"). Today we already know that ubiquitin serves to mark proteins in a process called ubiquitination or ubiquitinylation of a protein. The importance, variety and complex context of protein labeling with ubiquitin today reaches the level of the most significant post-translational modification of proteins, which is phosphorylation.

Inhibitory proteazomu
Proteasome inhibition leads to apoptosis of some tumor cells. Although the exact mechanism of their action on cells is not yet known, they are used as antitumor drugs. The most important representative is bortezomib State Agency for Drug Control: bortezomib, which is used for the treatment of multiple myeloma.

Related links

 * Degradation of proteins
 * Proteasome inhibitors/history
 * Proteasome/study
 * Proteasome/2. generation
 * Proteasome inhibitors/antabus
 * Lysosomes
 * Carcinogenesis
 * Proteasomes