This entry represents the ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier 1 (SUMO1) and similar proteins from animals. SUMO1 is a binding partner of the RAD51/52 nucleoprotein filament proteins, which mediate DNA strand exchange [, , ]. Its conjugation to cellular proteins has been implicated in multiple important cellular processes, such as nuclear transport, cell cycle control, oncogenesis, inflammation, and the response to virus infection [, , , ]. SUMO resembles ubiquitin (Ub) in structure, binding to other proteins and the mechanism of ligation. Ubiquitin (Ub) is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C terminus of Ub and the ε-amino group of a substrate lysine. SUMOs, like Ub, are covalently conjugated to lysine residues in a wide variety of target proteins in eukaryotic cells and regulate numerous cellular processes, such as transcription, epigenetic gene control, genomic instability, and protein degradation [, , ].
This entry represents E3 ubiquitin-protein ligase RNF8, which may be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. This enzyme promotes the formation of 'Lys-63'-linked polyubiquitin chains and functions with the specific ubiquitin-conjugating UBC13-MMS2 (UBE2N-UBE2V2) heterodimer [, ]. Substrates that are poly-ubiquitinated at 'Lys-63' are usually not targeted for degradation. RNF8 acts following DNA double-strand break (DSB) formation, and is recruited to the sites of damage by ATM-phosphorylated MDC1, where it promotes the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF) [, ]. It may play a role in the regulation of RXRA-mediated transcriptional activity, but is not involved in RXRA ubiquitination by UBE2E2.Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1, ), a ubiquitin-conjugating enzyme (E2, ), and a ubiquitin ligase (E3, , ), which work sequentially in a cascade. There are many different E3 ligases, which are responsible for the type of ubiquitin chain formed, the specificity of the target protein, and the regulation of the ubiquitinylation process []. Ubiquitinylation is an important regulatory tool that controls the concentration of key signalling proteins, such as those involved in cell cycle control, as well as removing misfolded, damaged or mutant proteins that could be harmful to the cell. Several ubiquitin-like molecules have been discovered, such as Ufm1 (), SUMO1 (), NEDD8, Rad23 (), Elongin B and Parkin (), the latter being involved in Parkinson's disease [].
PIAS3 is an E3-type small ubiquitin-like modifier (SUMO) ligases, stabilising the interaction between UBE2I and Ubc9 respectively and the substrate, and as a SUMO-tethering factor. It plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway and the steroid hormone signaling pathway [, , , ].PIAS3 sumoylates CCAR2, promoting its interaction with SIRT1 []and diminishes the sumoylation of ZFHX3 by preventing the colocalization of ZFHX3 with SUMO1 in the nucleus [].SUMO proteins are ubiquitin like proteins that are covalently attached to and detached from other proteins in cells to modify their function. SUMO is first activated in an ATP-dependent reaction by formation of a thioester bond with an E1 (SUMO-activating) enzyme and then transferred to the SUMO conjugating (E2) enzyme Ubc9. Ubc9 catalyses the formation of an isopeptide bond between the C-terminal of SUMO and the amino group of lysine in the target protein. Sumoylated proteins can be targeted for different cellular processes, such as nuclear transport, transcriptional regulation, apoptosis, and protein stability [].
Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1, ), a ubiquitin-conjugating enzyme (E2, ), and a ubiquitin ligase (E3, , ), which work sequentially in a cascade. There are many different E3 ligases, which are responsible for the type of ubiquitin chain formed, the specificity of the target protein, and the regulation of the ubiquitinylation process []. Ubiquitinylation is an important regulatory tool that controls the concentration of key signalling proteins, such as those involved in cell cycle control, as well as removing misfolded, damaged or mutant proteins that could be harmful to the cell. Several ubiquitin-like molecules have been discovered, such as Ufm1 (), SUMO1 (), NEDD8, Rad23 (), Elongin B and Parkin (), the latter being involved in Parkinson's disease [].Ubiquitin is a protein of 76 amino acid residues, found in all eukaryotic cells and whose sequence is extremely well conserved from protozoan to vertebrates. Ubiquitin acts through its post-translational attachment (ubiquitinylation) to other proteins, where these modifications alter the function, location or trafficking of the protein, or targets it for destruction by the 26S proteasome []. The terminal glycine in the C-terminal 4-residue tail of ubiquitin can form an isopeptide bond with a lysine residue in the target protein, or with a lysine in another ubiquitin molecule to form a ubiquitin chain that attaches itself to a target protein. Ubiquitin has seven lysine residues, any one of which can be used to link ubiquitin molecules together, resulting in different structures that alter the target protein in different ways. It appears that Lys(11)-, Lys(29) and Lys(48)-linked poly-ubiquitin chains target the protein to the proteasome for degradation, while mono-ubiquitinylatedand Lys(6)- or Lys(63)-linked poly-ubiquitin chains signal reversible modifications in protein activity, location or trafficking []. For example, Lys(63)-linked poly-ubiquitinylation is known to be involved in DNA damage tolerance, inflammatory response, protein trafficking and signal transduction through kinase activation []. In addition, the length of the ubiquitin chain alters the fate of the target protein. Regulatory proteins such as transcription factors and histones are frequent targets of ubquitinylation [].
Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1, ), a ubiquitin-conjugating enzyme (E2, ), and a ubiquitin ligase (E3, , ), which work sequentially in a cascade. There are many different E3 ligases, which are responsible for the type of ubiquitin chain formed, the specificity of the target protein, and the regulation of the ubiquitinylation process []. Ubiquitinylation is an important regulatory tool that controls the concentration of key signalling proteins, such as those involved in cell cycle control, as well as removing misfolded, damaged or mutant proteins that could be harmful to the cell. Several ubiquitin-like molecules have been discovered, such as Ufm1 (), SUMO1 (), NEDD8, Rad23 (), Elongin B and Parkin (), the latter being involved in Parkinson's disease [].Ubiquitin is a protein of 76 amino acid residues, found in all eukaryotic cells and whose sequence is extremely well conserved from protozoan to vertebrates. Ubiquitin acts through its post-translational attachment (ubiquitinylation) to other proteins, where these modifications alter the function, location or trafficking of the protein, or targets it for destruction by the 26S proteasome []. The terminal glycine in the C-terminal 4-residue tail of ubiquitin can form an isopeptide bond with a lysine residue in the target protein, or with a lysine in another ubiquitin molecule to form a ubiquitin chain that attaches itself to a target protein. Ubiquitin has seven lysine residues, any one of which can be used to link ubiquitin molecules together, resulting in different structures that alter the target protein in different ways. It appears that Lys(11)-, Lys(29) and Lys(48)-linked poly-ubiquitin chains target the protein to the proteasome for degradation, while mono-ubiquitinylated and Lys(6)- or Lys(63)-linked poly-ubiquitin chains signal reversible modifications in protein activity, location or trafficking []. For example, Lys(63)-linked poly-ubiquitinylation is known to be involved in DNA damage tolerance, inflammatory response, protein trafficking and signal transduction through kinase activation []. In addition, the length of the ubiquitin chain alters the fate of the target protein. Regulatory proteins such as transcription factors and histones are frequent targets of ubquitinylation [].This entry represents the conserved region at the centre of the Ubiquitin sequence.
