A Ubiquitin-Clathrin Connection?

Science's STKE  02 Apr 2002:
Vol. 2002, Issue 126, pp. tw126
DOI: 10.1126/stke.2002.126.tw126

Some proteins that are internalized into cellular clathrin-coated pits get modified on their intracellular domain with a single molecule of ubiquitin. Polo et al. now show that several proteins involved in regulating endocytosis also get monoubiquitinated. A ubiquitin interaction motif (UIM) was identified in eps15, eps15R, HRS, and epsin, proteins that interact directly or indirectly with clathrin. By expressing mutant forms of eps15 and eps15R in cells, the authors show that their UIM regions are required for both ubiquitination and for their ability to interact with ubiquitin. The authors proposed that UIM-ubiquitin interactions may regulate the endocytic process by assembling macrocomplexes of the endocytic machinery and membrane cargo. They also propose that once a protein with an UIM is monoubiquitinated, the UIM could bind to the ubiquitin group, possibly present on another protein, and prevent further ubiquitination.

S. Polo, S. Sigismund, M. Faretta, M. Guidi, M. R. Capua, G. Bossi, H. Chen, P. De Camilli, P. P. Di Fiore, A single motif responsible for ubiquitin recognition and monoubiquitnation in endocytic proteins. Nature 416: 451-455 (2002). [Online Journal]