Biomaterial Database

Probing ubiquitin and SUMO conjugation and deconjugation. 2018

Huib Ovaa, and Alfred C O Vertegaal

Oncode Institute, Leiden University Medical Center, 2300 RC Leiden, The Netherlands h.ovaa@lumc.nl vertegaal@lumc.nl.

Ubiquitin (Ub) and ubiquitin-like (Ubl) proteins including small Ubl modifier (SUMO) are small proteins which are covalently linked to target proteins to regulate their functions. In this review, we discuss the current state of the art and point out what we feel this field urgently needs in order to delineate the wiring of the system. We discuss what is needed to unravel the connections between different components of the conjugation machineries for ubiquitylation and SUMOylation, and to unravel the connections between the conjugation machineries and their substrates. Chemical probes are key tools to probe signal transduction by these small proteins that may help understand their action. This rapidly moving field has resulted in various small molecules that will help us to further understand Ub and SUMO function and that may lead to the development of new drugs.

UI	MeSH Term	Description	Entries
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D015335	Molecular Probes	A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in MOLECULAR GENETICS to detect the presence of a complementary sequence by NUCLEIC ACID HYBRIDIZATION.	Molecular Probe,Probe, Molecular,Probes, Molecular
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D054875	Ubiquitination	The act of ligating UBIQUITINS to PROTEINS to form ubiquitin-protein ligase complexes to label proteins for transport to the PROTEASOME ENDOPEPTIDASE COMPLEX where proteolysis occurs.	Ubiquitylation
D058207	Sumoylation	A type of POST-TRANSLATIONAL PROTEIN MODIFICATION by SMALL UBIQUITIN-RELATED MODIFIER PROTEINS (also known as SUMO proteins).	SUMO-Conjugation,SUMO Conjugation,SUMO-Conjugations,Sumoylations
D025801	Ubiquitin	A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.	APF-1,ATP-Dependent Proteolysis Factor 1,HMG-20,High Mobility Protein 20,Ubiquitin, Human,ATP Dependent Proteolysis Factor 1,Human Ubiquitin
D025841	Small Ubiquitin-Related Modifier Proteins	A class of structurally related proteins of 12-20 kDa in size. They covalently modify specific proteins in a manner analogous to UBIQUITIN.	SUMO Proteins,Sentrin Proteins,Sentrins,Ubiquitin-Related Modifier Protein, Small,Small Ubiquitin Related Modifier Proteins,Ubiquitin Related Modifier Protein, Small