Disease relevance of Rnf2

• Results suggest that Rae28/Ph1 and Ring1B dissociate from the chromatin upon its condensation in mitotic prophase in the U2-OS human osteosarcoma cell line [1].

High impact information on Rnf2

• Polycomb group proteins Ring1b and Bmi1 (B-cell-specific Moloney murine leukaemia virus integration site 1) are critical components of the chromatin modulating PRC1 complex [2].
• However, functional Ring1b is recruited by Xist and mediates ubiquitination of histone H2A in Eed deficient embryonic stem (ES) cells, which lack histone H3 lysine 27 tri-methylation [3].
• Ring1A and Ring1B display blocks of similarity throughout their sequences, including an N-terminal RING finger domain [4].
• Furthermore, we have identified two murine proteins, Ring1A and Ring1B, that interact directly with the repressor domain of M33 [4].
• Rnf2 (Ring1b) deficiency causes gastrulation arrest and cell cycle inhibition [5].

Biological context of Rnf2

• These results, together with the genetic interactions observed in compound Ring1B/Mel18 mutant mice, are consistent with a role for Ring1B in the regulation of Hox gene expression by Polycomb group complexes [6].
• On the inactive X chromosome, uH2A was maintained in Ring1A or Ring1B null cells, but not in double knockout cells, demonstrating an overlapping function for these proteins in development [7].
• We demonstrate that the enrichment of Ring1b and ubH2A on Xi is transient during TS and ES cell differentiation, suggesting that the Ring1b and ubH2A are involved in the initiation of both imprinted and random X inactivation [8].
• During maturation of oocytes, significant alterations of Rae28/Ph1 and Ring1B localization are concordant with configuration changes of the chromatin at the germinal vesicle stage of meiotic prophase [1].
• Importantly, dissociation of Rae28/Ph1 and Ring1B from the chromatin temporally correlates with transcriptional arrest both in mitosis and meiosis [1].

Anatomical context of Rnf2

• By contrast, the overexpression of Ring1B in chick embryos results in the repression of Hoxb9 expression in the neural tube [6].
• We found that the H2A-K119 ubiquitin E3 ligase Ring1b, a Polycomb group protein, is enriched on Xi in female trophoblast stem (TS) cells as well as differentiating embryonic stem (ES) cells [8].
• In this study, we analyzed subcellular localization of Rae28/Ph1 and Ring1B by using newly generated monoclonal antibodies in mitotic somatic cells and meiotic mouse oocytes [1].

Physical interactions of Rnf2

• The Bmi-1 oncoprotein interacts with dinG and MPh2: the role of RING finger domains [9].

Co-localisations of Rnf2

• Immunofluorescent staining by the antibodies has shown that endogenous Ring1B proteins clearly co-localize with Ring1A at the pattern of diffuse nuclear speckles [10].

Other interactions of Rnf2

• The data suggest a model whereby Bmi-1, dinG, and MPh2 form a stable heterotrimeric complex in which each protein contributes to the binding of the others [9].
• Together with their sequence similarity, Ring1B also may function as a Pc-G protein [10].

References