DUBs play several roles in the ubiquitin pathway.
One of the best characterised functions of DUBs is the removal of monoubiqutin and polyubiquitin chains from proteins.
These modifications are a post translational modification (addition to a protein after it has been made) where single ubiquitin proteins or chains of ubiquitin are added to lysines of a substrate protein.
These ubiquitin modifications are added to proteins by the ubiquitination machinery; ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s).
The end result is ubiquitin bound to lysine residues via an isopeptide bond.
Proteins are affected by these modifications in a number of ways: they regulate the degradation of proteins via the proteasome and lysosome; coordinate the cellular localisation of proteins; activate and inactivate proteins; and modulate protein-protein interactions.
DUBs play the antagonistic role in this axis by removing these modifications, therefore reversing the fate of the proteins.
In addition, a less understood role of DUBs is the cleavage of ubiquitin-like proteins such as SUMO and NEDD8.
Some DUBs may have the ability to cleave isopeptide bonds between these proteins and substrate proteins.

They activate ubiquitin by the proteolysis (breaking down) of the inactive expressed forms of ubiquitin.
Ubiquitin is encoded in mammals by 4 different genes: UBA52, RPS27A, UBB and UBC.
A similar set of genes is found in other eukaryotes such as yeast.
The UBA52 and RPS27A genes produce ubiquitin that is fused to ribosomal proteins and the UBB and UBC genes produce polyubiquitin (a chain of ubiquitin joined by their C- and N-termini).
DUBs cleave the ubiquitin from these proteins, producing active single units of ubiquitin.

DUBs also cleave single ubiquitin proteins that may have had their C-terminal tails accidentally bound to small cellular nucleophiles.
These ubiquitin-amides and ubiquitin-thioesters may be formed during standard ubiquitination reactions by the E1-E2-E3 cascade.
Glutathione and polyamines are two nucleophiles that might attack the thiolester bond between ubiquitin and these enzymes.
Ubiquitin C-terminal hydrolase is an example of the DUB that hydrolyses these bonds with broad specificity.

Free polyubiquitin chains are cleaved by DUBs to produce monoubiquitin.
The chains may be produced by the E1-E2-E3 machinery in the cell free from any substrate protein.
Another source of free polyubiquitin is the product of ubiquitin-substrate cleavage.
If DUBs cleave the base of the polyubiquitin chain that is attached to a protein, the whole chain will become free and needs to be recycled by DUBs.
DUBs play several roles in the ubiquitin pathway. One of the best characterised functions of DUBs is the removal of monoubiqutin and polyubiquitin chains from proteins. These modifications are a post translational modification (addition to a protein after it has been made) where single ubiquitin proteins or chains of ubiquitin are added to lysines of a substrate protein. These ubiquitin modifications are added to proteins by the ubiquitination machinery; ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s). The end result is ubiquitin bound to lysine residues via an isopeptide bond. Proteins are affected by these modifications in a number of ways: they regulate the degradation of proteins via the proteasome and lysosome; coordinate the cellular localisation of proteins; activate and inactivate proteins; and modulate protein-protein interactions. DUBs play the antagonistic role in this axis by removing these modifications, therefore reversing the fate of the proteins. In addition, a less understood role of DUBs is the cleavage of ubiquitin-like proteins such as SUMO and NEDD8. Some DUBs may have the ability to cleave isopeptide bonds between these proteins and substrate proteins.
They activate ubiquitin by the proteolysis (breaking down) of the inactive expressed forms of ubiquitin. Ubiquitin is encoded in mammals by 4 different genes: UBA52, RPS27A, UBB and UBC. A similar set of genes is found in other eukaryotes such as yeast. The UBA52 and RPS27A genes produce ubiquitin that is fused to ribosomal proteins and the UBB and UBC genes produce polyubiquitin (a chain of ubiquitin joined by their C- and N-termini). DUBs cleave the ubiquitin from these proteins, producing active single units of ubiquitin.
DUBs also cleave single ubiquitin proteins that may have had their C-terminal tails accidentally bound to small cellular nucleophiles. These ubiquitin-amides and ubiquitin-thioesters may be formed during standard ubiquitination reactions by the E1-E2-E3 cascade. Glutathione and polyamines are two nucleophiles that might attack the thiolester bond between ubiquitin and these enzymes. Ubiquitin C-terminal hydrolase is an example of the DUB that hydrolyses these bonds with broad specificity.
Free polyubiquitin chains are cleaved by DUBs to produce monoubiquitin. The chains may be produced by the E1-E2-E3 machinery in the cell free from any substrate protein. Another source of free polyubiquitin is the product of ubiquitin-substrate cleavage. If DUBs cleave the base of the polyubiquitin chain that is attached to a protein, the whole chain will become free and needs to be recycled by DUBs.
Deubiquitinating enzyme