KEGG   PATHWAY: ko03050
ko03050                     Pathway                                
The proteasome is a protein-destroying apparatus involved in many essential cellular functions, such as regulation of cell cycle, cell differentiation, signal transduction pathways, antigen processing for appropriate immune responses, stress signaling, inflammatory responses, and apoptosis. It is capable of degrading a variety of cellular proteins in a rapid and timely fashion and most substrate proteins are modified by ubiquitin before their degradation by the proteasome. The proteasome is a large protein complex consisting of a proteolytic core called the 20S particle and ancillary factors that regulate its activity in various ways. The most common form is the 26S proteasome containing one 20S core particle and two 19S regulatory particles that enable the proteasome to degrade ubiquitinated proteins by an ATP-dependent mechanism. Another form is the immunoproteasome containing two 11S regulatory particles, PA28 alpha and PA28 beta, which are induced by interferon gamma under the conditions of intensified immune response. Other regulatory particles include PA28 gamma and PA200. Although PA28 gamma also belongs to a family of activators of the 20S proteasome, it is localized within the nucleus and forms a homoheptamer. PA28 gamma has been implicated in the regulation of cell cycle progression and apoptosis. PA200 has been identified as a large nuclear protein that stimulates proteasomal hydrolysis of peptides.
Genetic Information Processing; Folding, sorting and degradation
Pathway map
ko03050  Proteasome

Other DBs
GO: 0000502
K03033  26S proteasome regulatory subunit N3
K06693  26S proteasome regulatory subunit N4
K03035  26S proteasome regulatory subunit N5
K03036  26S proteasome regulatory subunit N6
K03037  26S proteasome regulatory subunit N7
K03038  26S proteasome regulatory subunit N8
K03039  26S proteasome regulatory subunit N9
K03030  26S proteasome regulatory subunit N11
K03031  26S proteasome regulatory subunit N12
K10881  26 proteasome complex subunit DSS1
K03029  26S proteasome regulatory subunit N10
K03028  26S proteasome regulatory subunit N1
K03032  26S proteasome regulatory subunit N2
K06691  26S proteasome regulatory subunit N13
K03061  26S proteasome regulatory subunit T1
K03062  26S proteasome regulatory subunit T2
K03066  26S proteasome regulatory subunit T6
K03064  26S proteasome regulatory subunit T4
K03065  26S proteasome regulatory subunit T5
K03063  26S proteasome regulatory subunit T3
K06696  proteasome activator subunit 1 (PA28 alpha)
K06697  proteasome activator subunit 2 (PA28 beta)
K06698  proteasome activator subunit 3 (PA28 gamma)
K06699  proteasome activator subunit 4
K13527  proteasome-associated ATPase
K03420  proteasome regulatory subunit
K02730  20S proteasome subunit alpha 1 [EC:]
K02726  20S proteasome subunit alpha 2 [EC:]
K02728  20S proteasome subunit alpha 3 [EC:]
K02731  20S proteasome subunit alpha 4 [EC:]
K02729  20S proteasome subunit alpha 5 [EC:]
K02725  20S proteasome subunit alpha 6 [EC:]
K02727  20S proteasome subunit alpha 7 [EC:]
K02738  20S proteasome subunit beta 1 [EC:]
K02739  20S proteasome subunit beta 2 [EC:]
K02735  20S proteasome subunit beta 3 [EC:]
K02734  20S proteasome subunit beta 4 [EC:]
K02737  20S proteasome subunit beta 5 [EC:]
K02732  20S proteasome subunit beta 6 [EC:]
K02736  20S proteasome subunit beta 7 [EC:]
K02741  20S proteasome subunit beta 9 [EC:]
K02733  20S proteasome subunit beta 10 [EC:]
K02740  20S proteasome subunit beta 8 [EC:]
K11598  20S proteasome subunit beta 11 [EC:]
K03432  proteasome alpha subunit [EC:]
K03433  proteasome beta subunit [EC:]
K04687  interferon gamma
K06700  proteasome inhibitor subunit 1 (PI31)
K11599  proteasome maturation protein
Hirano Y, Murata S, Tanaka K
Large- and small-scale purification of mammalian 26S proteasomes.
Methods Enzymol 399:227-40 (2005)
Saeki Y, Tanaka K
Cell biology: two hands for degradation.
Nature 453:460-1 (2008)
Smith DM, Benaroudj N, Goldberg A
Proteasomes and their associated ATPases: a destructive combination.
J Struct Biol 156:72-83 (2006)
Strehl B, Seifert U, Kruger E, Heink S, Kuckelkorn U, Kloetzel PM
Interferon-gamma, the functional plasticity of the ubiquitin-proteasome system, and MHC class I antigen processing.
Immunol Rev 207:19-30 (2005)
Darwin KH
Prokaryotic ubiquitin-like protein (Pup), proteasomes and pathogenesis.
Nat Rev Microbiol 7:485-91 (2009)
Tomko RJ Jr, Hochstrasser M
Molecular architecture and assembly of the eukaryotic proteasome.
Annu Rev Biochem 82:415-45 (2013)
Budenholzer L, Cheng CL, Li Y, Hochstrasser M
Proteasome Structure and Assembly.
J Mol Biol 429:3500-3524 (2017)
Cloos J, Roeten MS, Franke NE, van Meerloo J, Zweegman S, Kaspers GJ, Jansen G
(Immuno)proteasomes as therapeutic target in acute leukemia.
Cancer Metastasis Rev 36:599-615 (2017)
Sakata E, Bohn S, Mihalache O, Kiss P, Beck F, Nagy I, Nickell S, Tanaka K, Saeki Y, Forster F, Baumeister W
Localization of the proteasomal ubiquitin receptors Rpn10 and Rpn13 by electron cryomicroscopy.
Proc Natl Acad Sci U S A 109:1479-84 (2012)
ko04120  Ubiquitin mediated proteolysis

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