Reactome | Antigen processing: Ubiquitination & Proteasome degradation

Antigen processing: Ubiquitination & Proteasome degradation

Stable Identifier

R-HSA-983168

Type

Pathway

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Antigen processing: Ubiquitination & Proteasome degradation

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Intracellular foreign or aberrant host proteins are cleaved into peptide fragments of a precise size, such that they can be loaded on to class I MHC molecules and presented externally to cytotoxic T cells. The ubiquitin-26S proteasome system plays a central role in the generation of these class I MHC antigens.
Ubiquitination is the mechanism of adding ubiquitin to lysine residues on substrate protein leading to the formation of a polyubiquitinated substrate. This process involves three classes of enzyme, an E1 ubiquitin-activating enzyme, an E2 ubiquitin-conjugating enzyme, and an E3 ubiquitin ligase. Polyubiquitination through lysine-48 (K48) generally targets the substrate protein for proteasomal destruction. The protease responsible for the degradation of K48-polyubiquitinated proteins is the 26S proteasome. This proteasome is a two subunit protein complex composed of the 20S (catalytic core particle) and 19S (regulatory particle) proteasome complexes. The proteasome eliminates most of the foreign and non-functional proteins from the cell by degrading them into short peptides; only a small fraction of the peptides generated are of the correct length to be presented by the MHC class I system. It has been calculated that between 994 and 3122 protein molecules have to be degraded for the formation of a single, stable MHC class I complex at the cell surface, with an average efficiency of 1 in 2000 (Kloetzel et al. 2004, Princiotta et al. 2003).

Literature References

PubMed ID	Title	Journal	Year
11917093	The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction Glickman, MH, Ciechanover, A	Physiol Rev	2002
17145306	Antigen presentation and the ubiquitin-proteasome system in host-pathogen interactions Ploegh, HL, Loureiro, J	Adv Immunol	2006
20351195	Characterizing the specificity and cooperation of aminopeptidases in the cytosol and endoplasmic reticulum during MHC class I antigen presentation Rock, KL, Hearn, A, York, IA, Bishop, C	J Immunol	2010
12648452	Quantitating protein synthesis, degradation, and endogenous antigen processing Buttgereit, F, Bennink, JR, Qian, SB, Yewdell, JW, Finzi, D, Schuchmann, S, Gibbs, J, Princiotta, MF	Immunity	2003
19489725	RING domain E3 ubiquitin ligases Deshaies, RJ, Joazeiro, CA	Annu Rev Biochem	2009
14734113	Proteasome and peptidase function in MHC-class-I-mediated antigen presentation Ossendorp, F, Kloetzel, PM	Curr Opin Immunol	2004