Protein degradation intracellular

Proteins are degraded by both ATP-dependent and ATP-independent pathways. Ubiquitin targets many intracellular proteins for degradation. Liver cell surface receptors bind and internalize circulating asialoglycoproteins destined for lysosomal degradation. 

Akagi T, Shima F, Akashi M (2011) Intracellular degradation and distribution of protein-encapsulated amphiphilic poly(amino acid) nanoparticles. Biomaterials 32 4959 1967... 

Edbauer, D., Willem, M., Lammich, S., Steiner, H., Haass, C. (2002) Insuhn-degrading enzyme rapidly removes the P-amyloid precursor protein intracellular domain (AlCD). J. Biol. Chem., Ill, 13389-13393. 

Formation of antigens from the intracellular degradation of pathogens The proteolytic system hydrolyses proteins of pathogens that are present within the host cell (e.g. a virus), to produce a short peptide which forms a complex with a specific protein, known as the major histocompatibility complex (MHC) protein. The peptide is, in fact, the antigen. At the plasma membrane, the MHC protein locates within the membrane and the small peptide sits on the outside of the membrane, where it can interact with the receptor on a cytotoxic T-lymphocyte to kill the host cell and the virus (Chapter 17). 

Multiubiquitination of intracellular proteins is a prerequisite for the selective degradation of intracellular proteins by the ubiquitin-dependent proteolytic pathway [236,237]. Monoubiquitinated histones are not degraded by the protea-some [238,239]. Proteasome, a multisubunit complex that catalyzes both ubiquitin-dependent and ubiquitin-independent protein degradation, is found in the cytoplasm and nucleus [240-242]. Thus, it is possible that multiubiquitination of the histones may tag these proteins for degradation. 

Some intracellular protein degradation (proteolysis) takes place in the lysosomes (see p. 234). In addition, there are protein complexes in the cytoplasm, known as pro-teasomes, in which incorrectly folded or old proteins are degraded. These molecules are recognized by a special marking (see p. 176). The proteasome also plays an important part in the presentation of antigens by immune cells (see p. 296). 

A modeT that accounts for the selective degradation of proteins based on the amino acid that is present on the amino- or N-end of nascent proteins. Intracellular processing of nascent, noncompartmentalized proteins generates the mature protein via the action of amino-terminal peptidases. In model studies using /3-galactosidase... 

Farris, W., Mansourian, S., Chang, Y., Linsley, L., Eckman, E. A., Frosch, M. P., Eckman, C. B., Tanzi, R. E., Selkoe, D. J., and Guennette, S. (2005). Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc. Natl. Acad. Sci. USA 100, 4162—4167. 

Class II MHC proteins present peptides to a class of lymphocytes known as helper lymphocytes, which stimulate antibody production against the peptides. In this case, the MHC associated peptides are derived by intracellular degradation of extracellular antigens imported into the cell. Association of a peptide foreign to... 

Calpains are preferentially involved in the degradation of proteins of the cytoskeleton. Although other proteolytic systems are also important for the removal of cytoskeletal proteins, the bulk of intracellular proteins are degraded by the proteasomal system [18]. This system is therefore the major proteolytic system involved in the degradation of proteins and in particular of oxidized proteins. The proteasomal system is often referred to as the ubiquitin-proteasome system due to its tight interaction with the ubiquitination machinery of the cell. 

Fig. 11 Fate of oxidized proteins. Intracellular oxidized proteins are degraded by the pro-...

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