Regulation of cell signalling by ubiquitylation

抄録

The attachment of a single ubiquitin, monoUb, to a substrate serves as an important regulatory modification implicated in receptor endocytosis, virus budding, gene transcription, DNA repair and replication, etc. The discovery of Ub-binding domains (UBDs), such as UBA, UIM, CUE and others, has indicated how monoUb can regulate such distinct cellular functions. We have cloned two new Ub-binding domains named UBM (Ub binding motif) and UBZ (Ub binding Zn finger) found in numerous cellular proteins. Their functional and biophysical characterization will be presented. In addition to binding Ub, several UBDs promote the monoubiquitylation of host proteins. We have recently shown that monoubiquitylation of the endocytic proteins Sts1, Sts2, Eps15 and Hrs facilitates intramolecular interactions with the UBDs, thus preventing them from binding to ubiquitylated cargoes. We mapped the in vivo monoubiquitylation site in Sts2 and demonstrated its functional importance for EGF receptor endocytosis. We propose that monoubiquitylation of Ub-binding proteins represent a general regulatory mechanism that inhibits their capacity to bind to and control functions of ubiquitylated targets in vivo. [J Physiol Sci. 2006;56 Suppl:S9]