| 1997 |
RING1 co-immunoprecipitates with human Polycomb homolog, BMI1, and HPH1, colocalizes with these PcG proteins in nuclear domains, and when targeted to a reporter gene acts as a transcriptional repressor. |
Co-immunoprecipitation, colocalization by immunofluorescence, reporter gene repression assay, yeast two-hybrid screen |
Molecular and cellular biology |
High |
9199346
|
| 1999 |
RING1 self-associates and directly interacts with BMI1 through distinct domains; overexpression of RING1 represses En-2 (a Polycomb target gene) and deregulates c-jun and c-fos, leading to oncogenic transformation (anchorage-independent growth and tumor formation in athymic mice). |
Yeast two-hybrid, in vitro protein-protein interaction assay, mammalian overexpression, anchorage-independent growth assay, nude mouse tumor assay |
Molecular and cellular biology |
High |
9858531
|
| 2000 |
HPC3 (human Polycomb 3) was identified as a direct binding partner of RING1 via the HPC3 C-box domain; this interaction in vivo required covalently modified forms of RING1 but only partially depended on the RING finger of RING1. |
Yeast two-hybrid screen using RING1 as bait, in vivo co-immunoprecipitation, domain-deletion analysis, reporter gene silencing assay |
The Journal of biological chemistry |
Medium |
10825164
|
| 2004 |
RING1 interacts with the LIM domains of KyoT2 in yeast and mammalian cells; a three-molecule complex of RBP-J, KyoT2, and RING1 forms in cells (RING1 and RBP-J do not associate directly). Overexpression of RING1 together with KyoT2 inhibits RBP-J transactivation by Notch intracellular domain (NIC), and this suppression is dependent on RING1's association with KyoT2. |
Yeast two-hybrid, in vitro binding, co-immunoprecipitation, reporter transactivation assay with overexpression and competition |
Nucleic acids research |
Medium |
14999091
|
| 2004 |
Drosophila Ring/Sce is the ortholog of mammalian Ring1/Ring1A; murine Ring1/Ring1A can rescue the extreme Polycomb phenotype caused by loss of maternal and zygotic Sce, demonstrating functional conservation. Drosophila Ring/Sce binds ~100 sites on polytene chromosomes, 70% overlapping with other PcG proteins, and directly interacts with PcG proteins. |
Genetic rescue (ectopic expression), polytene chromosome immunostaining, direct protein interaction assay |
Mechanisms of development |
High |
15147763
|
| 2006 |
Genetic epistasis in mice shows that Ring1/Ring1A deficiency reduces penetrance of homeotic transformations caused by YY1 heterozygosity; YY1 forms complexes with Ring1 and other class II PcG proteins (Rnf2, Bmi1) in GST pull-down experiments, establishing a direct physical and genetic interaction. |
Genetic epistasis in compound mutant mice, GST pull-down in transfected cells |
Mechanisms of development |
Medium |
16624538
|
| 2007 |
Conditional deletion of Ring1A and Ring1B (RING1 proteins) in mouse ES cells leads sequentially to loss of H2A ubiquitination, release of Ser5-phosphorylated (poised) RNAP II from bivalent developmental gene promoters, and subsequent gene de-repression, establishing that PRC1-mediated H2A ubiquitination enforces the poised RNAP II configuration at bivalent genes. |
Conditional genetic deletion (Ring1A/B knockout), ChIP for histone modifications and RNAP II phospho-isoforms, RT-PCR for gene expression |
Nature cell biology |
High |
18037880
|
| 2017 |
RING1 acts as an E3 ubiquitin ligase that directly interacts with p53 and ubiquitinates it, targeting p53 for proteasome-dependent degradation; the RING domain of RING1 is required for this E3 Ub ligase activity. RING1 depletion in p53 wild-type cancer cells induces cell-cycle arrest, apoptosis, and senescence, and this growth-inhibitory effect is partially rescued by p53 silencing, establishing a PRC1-independent function. |
Co-immunoprecipitation, in vitro ubiquitination assay, domain mutagenesis (RING domain), RNAi knockdown with cell-cycle/apoptosis/senescence readouts, p53 rescue experiment |
Cancer research |
High |
29187402
|
| 2018 |
A de novo RING1 missense mutation (p.R95Q) in the catalytic RING domain retains capacity to catalyze ubiquitin chain formation but is specifically defective in ubiquitylating histone H2A in nucleosomes; patient cells showed decreased H2A monoubiquitylation. In C. elegans, the equivalent missense or knockout of spat-3 (RING1 ortholog) abolished H2A monoubiquitylation and caused neuronal migration and axon guidance defects. |
In vitro ubiquitination assay (wild-type vs. mutant RING1), patient cell H2Aub measurement, CRISPR knock-in in C. elegans, neuronal phenotype analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
29386386
|
| 2020 |
RING1B (and RING1A+B together) binds BMP and Wnt ligand gene loci in the ventral telencephalon and is required for their repression; deletion of Ring1b (or Ring1a/b) in neuroepithelial cells causes ectopic dorsal gene expression and loss of Shh expression in the ventral region, establishing a role for RING1 in dorsoventral patterning through region-specific PcG-mediated repression of BMP/Wnt signaling. |
Conditional gene knockout in mice, ChIP for Ring1B binding and H3K27me3 at target loci, in situ hybridization/immunostaining for gene expression |
Nature communications |
High |
33177537
|
| 2015 |
RING1 proteins (RING1A/RING1B) repress Meis2 (and Meis1) in the proximal forelimb bud; deletion of Ring1A/B causes failure to repress proximal Meis1/2 and defects in distal limb specification. Additional deletion of Meis2 partially restores distal gene expression and limb formation in Ring1A/B-deficient mice, establishing a genetic epistasis relationship (RING1 → Meis2 repression → distal specification). |
Conditional double knockout in mice, genetic epistasis (Meis2 deletion rescue), ChIP for Ring1B binding at Meis1/2 loci |
Development (Cambridge, England) |
High |
26674308
|
| 2024 |
RING1 directly interacts with GSDMD and ubiquitinates it at K51 and K168 via K48-linked chains, promoting proteasomal degradation of GSDMD and thereby negatively regulating pyroptosis. Loss of Ring1 increased bacterial infectious load and exacerbated LPS-induced sepsis in vivo; inhibition of RING1 E3 ligase activity (by mutation or small molecule inhibitors) increased GSDMD levels and pyroptotic cell death. |
Co-immunoprecipitation, in vitro ubiquitination assay, site-directed mutagenesis (K51/K168), RING domain inhibition, Ring1 knockout mice with infection/sepsis models |
Cell death and differentiation |
High |
40369166
|
| 2024 |
RING1 (harboring a hypomorphic missense variant) binds target loci but fails to catalyze H2AK119ub1, reducing H2AK119ub1 by preventing catalytically active complexes from accessing the locus. Reduced H2AK119ub1 due to hypomorphic RING1 delays DNA damage repair and cell cycle progression in neural progenitor cells (NPCs) but does not generate differential gene expression impacting NPC differentiation; in contrast hypomorphic RNF2 reduces H2AK119ub1 more broadly and affects both DNA repair and transcription. |
In vitro neurodevelopment model, ChIP-seq for H2AK119ub1, DNA damage repair assays, cell cycle analysis, transcriptome analysis; CRISPR-introduced hypomorphic variants |
Nature communications |
High |
39256363
|
| 2017 |
CD147 interacts with RING1 through CD147's transmembrane domain (identified by yeast two-hybrid); RING1 inhibits CD147's ability to promote melanoma cell migration, and CD147 localizes to the nuclear envelope in melanoma cells. |
Yeast two-hybrid, co-immunoprecipitation, migration assay with RING1 overexpression |
PloS one |
Low |
28832687
|
| 2026 |
RING1 acts as an E3 ubiquitin ligase for Integrin α5 in ESCC cells, binding and destabilizing Integrin α5 via K11-linked ubiquitination in a RING domain-dependent manner; overexpression of RING1 degrades Integrin α5 and suppresses FAK pathway activity, cell adhesion, spreading, and migration; re-expression of Integrin α5 rescues RING1-mediated suppression. |
Co-immunoprecipitation, ubiquitination assay, domain-deletion analysis (catalytic domain), Integrin α5 re-expression rescue, adhesion/migration assays, in vivo metastasis model |
Cellular signalling |
Medium |
42229736
|