The polycomb -interacting protein Rybp is a ubiquitin and a SUMO binding protein
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Numerous receptor proteins have been identified that are capable of recognizing other proteins that have been modified by ubiquitin or SUMO. It is thought that the sensing and interpretation of these modifications by the receptors enables changes in function or localization of the modified proteins. Here we show that the Polycomb Group (PcG)-interacting protein Rybp can recognize ubiquitin- and SUMO-modified proteins; this is mediated by its amino-terminal NZF-type of ubiquitin binding domain (UBD) and carboxy-terminal SUMO binding motif (SBM). Rybp itself can also undergo post-translational modification by both ubiquitin and SUMO, and a coupling mechanism exists between Rybp's activity as a ubiquitin and SUMO binding protein and its post-translational modification by these small polypeptides. Members of the PcG family that are known E3 ligases, namely Ring1B and Pc2, can enhance Rybp ubiquitination and sumoylation status, respectively.;Our data indicate that ubiquitinated-histone H2A is a target for Rybp's ubiquitin binding activity; interestingly, histone H2A is also a substrate for Ring1B's ubiquitin E3 ligase activity. Consistent with this binding, Rybp is enriched with Ring1B on the inactive X chromosome in trophoblast stem cells, whereupon histone H2A ubiquitination has previously been shown to be an epigenetic marker. Accordingly, the basis for Rybp's interaction with PcG proteins relates in part to their catalytic activity towards Rybp, but also appears to converge upon histone modification associated with gene silencing.;In a separate study, we show that the Myc antagonist Mxi1, which has previously been shown by our laboratory to be a novel Rybp-interacting partner, is both sumoylated and ubiquitinated. Future studies are necessary to resolve whether Rybp senses Mxi1's post-translational modification status, and to identify the full spectrum of targets for Rybp.;To our knowledge, Rybp is the first example of a factor that is capable of recognizing ubiquitinated and sumoylated proteins. This dual property is likely more widespread, and may provide a means for ubiquitin/SUMO binding proteins to enable communication between these two post-translational modifications.