E3 ubiquitin ligases ubiquitinate target proteins

Stable Identifier
R-HSA-8866654
Type
Pathway
Species
Homo sapiens
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E3 ubiquitin ligases catalyze the transfer of an ubiquitin from an E2-ubiquitin conjugate to a target protein. Generally, ubiquitin is transferred via formation of an amide bond to a particular lysine residue of the target protein, but ubiquitylation of cysteine, serine and threonine residues in a few targeted proteins has also been demonstrated (reviewed in McDowell and Philpott 2013, Berndsen and Wolberger 2014). Based on protein homologies, families of E3 ubiquitin ligases have been identified that include RING-type ligases (reviewed in Deshaies et al. 2009, Metzger et al. 2012, Metzger et al. 2014), HECT-type ligases (reviewed in Rotin et al. 2009, Metzger et al. 2012), and RBR-type ligases (reviewed in Dove et al. 2016). A subset of the RING-type ligases participate in CULLIN-RING ligase complexes (CRLs which include SCF complexes, reviewed in Lee and Zhou 2007, Genschik et al. 2013, Skaar et al. 2013, Lee et al. 2014).
Some E3-E2 combinations catalyze mono-ubiquitination of the target protein (reviewed in Nakagawa and Nakayama 2015). Other E3-E2 combinations catalyze conjugation of further ubiquitin monomers to the initial ubiquitin, forming polyubiquitin chains. (It may also be possible for some E3-E2 combinations to preassemble polyubiquitin and transfer it as a unit to the target protein.) Ubiquitin contains several lysine (K) residues and a free alpha amino group to which further ubiquitin can be conjugated. Thus different types of polyubiquitin are possible: K11 linked polyubiquitin is observed in endoplasmic reticulum-associated degradation (ERAD), K29 linked polyubiquitin is observed in lysosomal degradation, K48 linked polyubiquitin directs target proteins to the proteasome for degradation, whereas K63 linked polyubiquitin generally acts as a scaffold to recruit other proteins in several cellular processes, notably DNA repair (reviewed in Komander et al. 2009).

Literature References
PubMed ID Title Journal Year
23912815 The emerging family of CULLIN3-RING ubiquitin ligases (CRL3s): cellular functions and disease implications

Genschik, P, Sumara, I, Lechner, E

EMBO J. 2013
17588513 DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase

Lee, J, Zhou, P

Mol Cell 2007
27312108 Molecular insights into RBR E3 ligase ubiquitin transfer mechanisms

Dove, KK, Stieglitz, B, Duncan, ED, Rittinger, K, Klevit, RE

EMBO Rep. 2016
24699078 New insights into ubiquitin E3 ligase mechanism

Berndsen, CE, Wolberger, C

Nat. Struct. Mol. Biol. 2014
19754430 The emerging complexity of protein ubiquitination

Komander, D

Biochem. Soc. Trans. 2009
26085183 Protein monoubiquitylation: targets and diverse functions

Nakagawa, T, Nakayama, K

Genes Cells 2015
23732108 Non-canonical ubiquitylation: mechanisms and consequences

McDowell, GS, Philpott, A

Int. J. Biochem. Cell Biol. 2013
23657496 Mechanisms and function of substrate recruitment by F-box proteins

Skaar, JR, Pagan, JK, Pagano, M

Nat. Rev. Mol. Cell Biol. 2013
23747565 RING-type E3 ligases: master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination

Metzger, MB, Pruneda, JN, Klevit, RE, Weissman, AM

Biochim. Biophys. Acta 2014
19489725 RING domain E3 ubiquitin ligases

Deshaies, RJ, Joazeiro, CA

Annu Rev Biochem 2009
22389392 HECT and RING finger families of E3 ubiquitin ligases at a glance

Metzger, MB, Hristova, VA, Weissman, AM

J. Cell. Sci. 2012
19436320 Physiological functions of the HECT family of ubiquitin ligases

Rotin, D, Kumar, S

Nat. Rev. Mol. Cell Biol. 2009
23624913 SCFs in the new millennium

Lee, EK, Diehl, JA

Oncogene 2014
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