Distinct monoubiquitin signals in receptor endocytosis.
Numerous cellular proteins are post-translationally modified by the addition of the small modifier protein ubiquitin (Ub). The functional consequences of the type of ubiquitination vary, such that polyubiquitinated proteins are targeted for degradation by the proteasome, whereas monoubiquitination is implicated in other cellular functions, including endocytic trafficking and DNA repair. The monoubiquitination of trafficking cargoes, such as receptors and associated proteins, as well as of endocytic accessory Ub-binding proteins, raises the question of the precise function of monoubiquitin signals in the endocytic route. Recent biochemical and genetic evidence shows that multiple monoubiquitination of epidermal growth factor and platelet-derived growth factor receptors provides trafficking and sorting tags that ensure receptor endocytosis and degradation, whereas monoubiquitination of accessory proteins might play a role in regulating their function as Ub-receptors in the endosome.
Haglund
Kaisa
K
Institute of Biochemistry II, Goethe University Medical School, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.
Di Fiore
Pier Paolo
PP
Dikic
Ivan
I
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D021381:Protein Transport / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*
D009097:Multienzyme Complexes; D011956:Receptors, Cell Surface; D025801:Ubiquitin; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex