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Ubiquitination Cascade Pathway

Click on one of the buttons below to explore the ubiquitination process and the different types of ubiquitination that can be generated.

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Ubiquitin

Substrate

Monoubiquitination

Multi-monoubiquitination

K6-linked

DUB

K11-linked

DUB

K27-linked

DUB

K29-linked

DUB

K33-linked

DUB

K48-linked

DUB

K63-linked

DUB

Met1-linked
(linear)

DUB

Polyubiquitin

ER stress-mediated apoptosis
Lysosomal degradation
mRNP disassembly
Wnt/beta-Catenin signaling

Antiviral immunity
Mitochondrial transport
TGF-beta signaling
Ubiquitin fusion degradation

Cell cycle
ERAD
Hedgehog signaling
TNF RI signaling

DNA repair
Histone modification
Cell cycle

Protein trafficking
TCR signaling

Proteasomal degradation
TLR2/4 signaling
TCR signaling
Transcription regulation

Autophagy
Development
DNA replication and repair
Innate and adaptive immunity
Neurodegeneration
Signal transduction
Spliceosome function

Immunity

DNA replication and repair
Endocytosis
Signal transduction
Protein localization
Transcription regulation

Endocytosis
Signal transduction
Protein localization

PPi + AMP

ATP

Overview of Ubiquitination Cascade

Ubiquitin is a highly conserved globular 76-residue eukaryotic protein found in the cytoplasm and nucleus of cells. Ubiquitin can be covalently attached (conjugated) to proteins in a process termed ubiquitination that utilizes Ubiquitin-activating (E1), Ubiquitin-conjugating (E2) and Ubiquitin Ligase (E3) enzymes. Ubiquitination affects protein stability, subcellular localization, and the ability to interact with other proteins. Ubiquitin can be attached to substrate proteins in three different manners: monoubiquitination, multi-monoubiquitination, and polyubiquitination. Eight residues within ubiquitin can be utilized to form polyubiquitin chains [K6, K11, K27, K29, K33, K48, K63, and Met1 (linear)] and linkage type directs the modified proteins to different cellular fates. Polyubiquitin chains of all linkages listed above have been detected in vivo and have been shown to differentially affect many cellular processes, signaling pathways, and disease states. Boston Biochem reagents allow you to discover if a protein of interest is ubiquitinated and investigate how ubiquitination affects the function of that protein.

To learn more, please visit our Ubiquitin and Ubiquitin-like Modifiers Research Area.

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