Multiple roles of Ring 1 and YY1 binding protein in physiology and disease

Abstract

Ring 1 and YY1 binding protein (RYBP) was first identified in 1999, and its structure includes a conserved Npl4 Zinc finger motif at the N-terminus, a central region that is characteristically enriched with arginine and lysine residues and a C-terminal region enriched with serine and threonine amino acids. Over nearly 20 years, multiple studies have found that RYBP functions as an organ developmental adaptor. There is also evidence that RYBP regulates the expression of different genes involved in various aspects of biological processes, via a mechanism that is dependent on interactions with components of PcG complexes and/or through binding to different transcriptional factors. In addition, RYBP interacts directly or indirectly with apoptosis-associated proteins to mediate anti-apoptotic or pro-apoptotic activity in both the cytoplasm and nucleus of various cell types. Furthermore, RYBP has also been shown to act as tumour suppressor gene in different solid tumours, but as an oncogene in lymphoma and melanoma. In this review, we summarize our current understanding of the functions of this multifaceted RYBP in physiological and pathological conditions, including embryonic development, apoptosis and cancer, as well as its role as a component of polycomb repressive complex 1.

Keywords: RYBP; PRC1; apoptosis; cancer; development.

Figure 1

Schematic diagram of RYBP in different complexes. (A) The canonical PRC1 comprises four core proteins families: PCGF (PCGF1‐6), CBX (CBX2/4/6/7/8), PHC (PHC1/2/3) and RING1A/B. (B) The RYBP‐PRC1 complex comprises PCGF2, PHC1, RING1B and RYBP. (C) The RYBP‐BCOR complex comprises RING1A, RING1B, FBXL10, PCGF1, BCOR and RYBP. (D) RYBP also binds to transcription factors, including hGABPβ, E2F2, E2F3 and E2F6. The contacts illustrated in the diagrams do not represent the actual interactions.

Figure 2

Schematic diagram of RYBP in the context of apoptosis and cancer progression. Solid arrows indicate stimulatory effects. T bars indicate inhibitory effects. Details are described in the text. FADD, FAS‐associated death domain protein; JNK, c‐jun N‐terminal kinase; AP1, activator protein 1; DEDD, DED‐containing DNA‐binding protein; Hippi, Hip1 protein interactor; FANK1, fibronectin type III and ankyrin repeat domains 1; MDM2, mouse double minute 2; DIAP1, apoptosis protein 1.