The Rybp protein has been promoted as a Polycomb group (PcG)-associated protein, but its molecular function has remained elusive. Here we show that Rybp is a novel ubiquitin binding protein and is itself ubiquitinated. The Rybp interacting PcG protein Ring1B, a known ubiquitin E3 ligase, promotes Rybp ubiquitination. Moreover, one target of Rybp's ubiquitin binding domain appears to be ubiquitinated histone H2A; this histone is a substrate for Ring1B's E3 ligase activity in association with gene silencing processes. These findings on Rybp provide a further link between the ubiquitination system and PcG transcriptional repressors.
Bibliographical noteFunding Information:
The authors thank Drs. Jack Lenz, Ian Willis, Jon Warner, Richard Stanley, Liang Zhu, as well as members of the Schreiber-Agus laboratory, for stimulating discussions and critical reading of the manuscript. We are indebted to Dr. Jennifer Blanck for her contributions in the early phases of this study, Dr. Dmitry Fyodorov for helpful advice, and Dr. Cristina Montagna and the Albert Einstein Genome Imaging Facility for assistance in microscopy. Data in this paper are from a thesis submitted by RA in partial fulfillment of the requirements of the Degree of Doctor of Philosophy in the Graduate Division of Medical Sciences, Albert Einstein College of Medicine, Yeshiva University. This work was supported in part by Public Health Service Grants from the NIH: CA92558 (N.S.A.), CA71540 (V.J.B.), and AI51174 (W.I.S.). S.L.A. was supported in part by IRG 77-003-23 from the American Cancer Society. Funds from the New York Speaker’s Fund for Biomedical Research (N.S.A.), and support from the Albert Einstein Cancer Center (N.S.A.) are acknowledged as well.
- Histone H2A
- Polycomb group