EH and UIM: endocytosis and more.
Exogenously and endogenously originated signals are propagated within the cell by functional and physical networks of proteins, leading to numerous biological outcomes. Many protein-protein interactions take place between binding domains and short peptide motifs. Frequently, these interactions are inducible by upstream signaling events, in which case one of the two binding surfaces may be created by a posttranslational modification. Here, we discuss two protein networks. One, the EH-network, is based on the Eps15 homology (EH) domain, which binds to peptides containing the sequence Asp-Pro-Phe (NPF). The other, which we define as the monoubiquitin (mUb) network, relies on monoubiquitination, which is emerging as an important posttranslational modification that regulates protein function. Both networks were initially implicated in the control of plasma membrane receptor endocytosis and in the regulation of intracellular trafficking routes. The ramifications of these two networks, however, appear to extend into many other aspects of cell physiology as well, such as transcriptional regulation, actin cytoskeleton remodeling, and DNA repair. The focus of this review is to integrate available knowledge of the EH- and mUb networks with predictions of genetic and physical interactions stemming from functional genomics approaches.
Polo
Simona
S
Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy.
Confalonieri
Stefano
S
Salcini
Anna Elisabetta
AE
Di Fiore
Pier Paolo
PP
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D025801:Ubiquitin / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C486206:EPS15 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D025801:Ubiquitin