Affinage

RLIM

E3 ubiquitin-protein ligase RLIM · UniProt Q9NVW2

Length
624 aa
Mass
68.5 kDa
Annotated
2026-04-28
57 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RLIM (RNF12) is an X-linked RING-H2 E3 ubiquitin ligase that functions as a central dosage-sensitive regulator of X chromosome inactivation, transcriptional control, and developmental signaling by targeting diverse substrates for ubiquitin-dependent modification. Its best-characterized role is dose-dependent activation of Xist transcription through ubiquitination and proteasomal degradation of the Xist repressor REX1, a mechanism essential for imprinted XCI in pre-implantation embryos but dispensable for random XCI in the epiblast, where REX1 is independently downregulated (PMID:22596162, PMID:30420655, PMID:38113263, PMID:24870238). Beyond XCI, RLIM ubiquitinates Smad7, MDM2, BRF1, Stathmin, PML, and c-Myc to regulate TGF-β signaling, p53 stability, RNA polymerase III transcription, and cell proliferation, while also acting as a transcriptional corepressor by recruiting the Sin3A/HDAC complex to LIM homeodomain factors (PMID:10431247, PMID:22560923, PMID:26926424, PMID:30413534). RLIM undergoes AKT- and S214-phosphorylation-dependent nucleocytoplasmic shuttling, is stabilized by a USP26 feed-forward loop, and is recruited to chromatin via a non-catalytic basic region; loss-of-function RING domain mutations cause the X-linked intellectual disability syndrome TOKAS (PMID:29742418, PMID:35857630, PMID:38199845, PMID:23904271).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    Establishing RLIM's initial identity resolved how LIM homeodomain transcription factors are silenced: RLIM was shown to bind LIM domains and recruit Sin3A/HDAC corepressor complexes, defining it as a transcriptional corepressor rather than a conventional E3 ligase.

    Evidence Co-immunoprecipitation, transcriptional reporter assays, and in vivo chick wing overexpression

    PMID:10431247

    Open questions at the time
    • Whether the corepressor function requires RING-dependent catalytic activity was not tested
    • Endogenous substrate stoichiometry was not addressed
  2. 2009 High

    The discovery that RLIM dosage controls X chromosome inactivation initiation reframed RLIM from a transcriptional cofactor to a key developmental switch, answering how cells count X chromosomes.

    Evidence Transgenic overexpression and heterozygous knockout in mouse ES cells with Xist RNA FISH readouts

    PMID:19945382

    Open questions at the time
    • The direct substrate mediating XCI activation was unknown
    • Whether RLIM's E3 activity or a non-catalytic function was required was unresolved
  3. 2009 Medium

    Parallel work expanded RLIM's substrate repertoire beyond transcription factors: RLIM was shown to ubiquitinate TRF1 to regulate telomere length and to coactivate ERα at estrogen-responsive promoters, revealing context-dependent functions.

    Evidence Co-IP, shRNA knockdown, telomere length assays (TRF1); Co-IP from breast tumor tissue, ChIP on ERα targets (ERα)

    PMID:19117995 PMID:19164295

    Open questions at the time
    • TRF1 ubiquitination was not reconstituted with purified components
    • ERα coactivation mechanism (ubiquitin-dependent or -independent) was not resolved
  4. 2010 High

    Conditional knockout showed maternal RLIM is required for imprinted XCI (iXCI) but dispensable for random XCI (rXCI), separating RLIM's developmental functions into distinct temporal windows.

    Evidence Oocyte-specific Rnf12 conditional knockout mice with Xist RNA FISH and X-linked gene expression analysis

    PMID:20962847

    Open questions at the time
    • The molecular target through which maternal RLIM drives iXCI was not yet identified
    • Why RLIM is dispensable for rXCI was mechanistically unexplained
  5. 2012 High

    Identification of REX1 as the direct ubiquitination target solved the core XCI mechanism: RNF12 ubiquitinates REX1 for proteasomal degradation, relieving REX1-mediated Xist repression in a dose-dependent manner.

    Evidence In vitro ubiquitination reconstitution, ChIP-seq, Rnf12-KO ES cells, Rex1 overexpression/knockdown, Xist RNA FISH

    PMID:22596162

    Open questions at the time
    • Whether REX1 is the sole XCI-relevant target was not established
    • How RNF12 achieves substrate specificity for REX1 over other targets was unclear
  6. 2012 High

    Simultaneous identification of Smad7 as an RLIM substrate connected RLIM to TGF-β/BMP signaling and demonstrated its broader role as a multi-substrate E3 ligase in developmental signaling.

    Evidence In vitro ubiquitination, RNF12-KO ES cells with elevated Smad7, zebrafish gain/loss-of-function

    PMID:22560923

    Open questions at the time
    • Whether Smad7 and REX1 ubiquitination are regulated by distinct mechanisms was unknown
    • Tissue-specific prioritization among substrates was not addressed
  7. 2012 High

    RLIM was found to be essential for mammary alveolar cell survival during lactation, demonstrating a post-developmental, tissue-specific function for the paternally expressed allele.

    Evidence Conditional mammary gland Rnf12 knockout with pregnancy/lactation phenotyping and apoptosis assays

    PMID:22541433

    Open questions at the time
    • The direct substrate mediating alveolar cell survival was not identified
    • Whether this function depends on XCI or a direct signaling target was unresolved
  8. 2013 High

    Phosphorylation of S214 was shown to regulate RLIM nucleocytoplasmic shuttling, and blocking this shuttling abolished alveolar cell survival, establishing that regulated subcellular localization is essential for RLIM function.

    Evidence Phosphomimetic/phosphoresistant mutagenesis, live-cell imaging, mammary alveolar cell survival assays

    PMID:23904271

    Open questions at the time
    • The kinase responsible for S214 phosphorylation was not identified in this study
    • Whether shuttling regulates substrate access differentially was not tested
  9. 2014 High

    Definitive in vivo evidence showed RLIM is dispensable for random XCI in the epiblast, resolving the apparent contradiction between ES cell and in vivo studies and restricting RLIM's essential XCI role to imprinted XCI.

    Evidence Early conditional Rnf12 knockout mice with Xist FISH and H3K27me3 immunostaining in epiblast cells

    PMID:24870238

    Open questions at the time
    • What replaces RLIM function during rXCI was not identified
    • Whether residual RLIM protein contributes was not fully excluded
  10. 2016 Medium

    RLIM was placed in the p53 regulatory network through its ubiquitination and degradation of MDM2, and shown to inhibit c-Myc transcriptional activity via non-degradative ubiquitination, broadening the functional consequences of RLIM-mediated ubiquitination beyond proteolysis.

    Evidence Yeast two-hybrid, Co-IP, in vivo ubiquitination assays, p53/Myc reporter assays, apoptosis and proliferation assays

    PMID:26926424 PMID:27684546

    Open questions at the time
    • MDM2 and c-Myc ubiquitination not reconstituted with purified components
    • Physiological relevance of these interactions not validated in vivo in animal models
    • Ubiquitin chain linkage type on c-Myc not determined
  11. 2018 High

    Patient TOKAS mutations were shown to specifically impair RLIM's E3 catalytic activity by disrupting the RING domain or a distal regulatory region, directly linking catalytic function to X-linked intellectual disability and establishing the disease mechanism.

    Evidence In vitro ubiquitination with XLID mutant proteins, ES cell and neural differentiation assays

    PMID:29742418

    Open questions at the time
    • Which specific substrates are most relevant to neurodevelopment was not determined
    • Structural basis for distal regulatory region function was not resolved
  12. 2018 High

    Double-knockout genetic epistasis (Rnf12−/−; Rex1−/−) definitively established REX1 as the critical in vivo target for both iXCI and rXCI: loss of REX1 fully rescued XCI and female viability in Rnf12-null mice.

    Evidence Double-knockout mouse genetics with iXCI and rXCI phenotyping, Xist RNA FISH

    PMID:30420655

    Open questions at the time
    • Whether non-REX1 targets contribute to RLIM's developmental roles outside XCI was not addressed
  13. 2021 High

    RLIM was shown to function in male germ cells during spermiogenesis, with knockout causing excess cytoplasm retention, decreased motility, and reduced fertility — a role independent of XCI.

    Evidence Systemic and spermatogenic cell-specific conditional Rnf12 knockout mice, sperm morphology and IVF assays

    PMID:33620316

    Open questions at the time
    • The direct spermiogenesis substrate(s) were not identified
    • Whether the sperm phenotype relates to known substrates like REX1 or Smad7 was unresolved
  14. 2022 High

    A feed-forward amplification loop was uncovered: RNF12 degrades REX1 to derepress Usp26, and USP26 deubiquitinates RNF12 to prevent its autoubiquitylation and stabilize it, amplifying RNF12 signaling during germ cell differentiation; TOKAS and infertility variants disrupt this loop.

    Evidence Quantitative proteomics, Co-IP, ubiquitination assays, Usp26 reporter assays, patient variant functional testing

    PMID:35857630

    Open questions at the time
    • Whether this feed-forward loop operates in somatic tissues beyond germ cells is unknown
    • Structural basis of USP26–RNF12 interaction not determined
  15. 2022 Medium

    AKT was identified as a kinase that phosphorylates RLIM to drive its nuclear localization and stabilization, accelerating Smad7 degradation and enhancing TGF-β-driven metastasis, connecting RLIM regulation to oncogenic PI3K/AKT signaling.

    Evidence Co-IP, phosphorylation assays, nuclear/cytoplasmic fractionation, zebrafish and murine xenograft metastasis models

    PMID:35013159

    Open questions at the time
    • Relationship between AKT-mediated and S214 phosphorylation not clarified
    • Whether AKT regulation of RLIM operates in normal development was not tested
  16. 2023 High

    The long-standing question of why RLIM is essential for iXCI but dispensable for rXCI was resolved: REX1 is independently downregulated in epiblast cells upon implantation, making RLIM's REX1-degradation activity unnecessary for rXCI.

    Evidence Mouse genetics with compartment-specific REX1 immunofluorescence in blastocysts and post-implantation embryos

    PMID:38113263

    Open questions at the time
    • What mechanism downregulates REX1 in epiblast cells independently of RLIM is unknown
  17. 2024 High

    Chromatin recruitment of RNF12 was shown to depend on a non-catalytic basic region recognizing a consensus DNA sequence motif, with an N-terminal autoinhibitory mechanism gating this interaction — explaining how RNF12 co-localizes with REX1 at target promoters for efficient ubiquitylation.

    Evidence ChIP-seq, BioID proximity proteomics, basic region mutagenesis, in vitro ubiquitination

    PMID:38199845

    Open questions at the time
    • Whether chromatin targeting selectivity differs across tissues or substrates is unknown
    • Structural details of the autoinhibitory mechanism are not resolved
    • Whether DNA binding contributes to non-REX1 substrate recognition is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the identity of RLIM substrates critical for neurodevelopment in TOKAS, the structural basis for autoinhibition and chromatin targeting, how substrate priority is determined across tissues, and whether the RNF12–USP26 amplification loop operates outside germ cells.
  • No structural model of full-length RLIM exists
  • Neurodevelopmental substrates remain unidentified
  • Tissue-specific substrate selectivity mechanisms are unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0140110 transcription regulator activity 2 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 8 R-HSA-392499 Metabolism of proteins 8 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1474165 Reproduction 1
Partners
BRF1MDM2MYCSMAD7TERF1USP26ZBTB17ZFP42

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 RLIM (RNF12) was identified as a RING-H2 zinc-finger protein that binds LIM domains and acts as a transcriptional corepressor by recruiting the Sin3A/histone deacetylase complex to LIM homeodomain transcription factors, inhibiting their functional activity. Co-immunoprecipitation, transcriptional reporter assays, in vivo chick wing overexpression Nature genetics High 10431247
2009 RNF12/RLIM functions as a dose-dependent, X-encoded activator of X chromosome inactivation (XCI); additional copies of Rnf12 trigger XCI in male ES cells, and heterozygous Rnf12+/- female ES cells show markedly reduced XCI initiation, dependent on an intact open reading frame. Transgenic overexpression in mouse ES cells, heterozygous knockout ES cells, differentiation assays monitoring Xist RNA Cell High 19945382
2009 RLIM directly interacts with TRF1 and targets it for ubiquitin-dependent proteasomal degradation, independently of Fbx4, thereby modulating telomere length; depletion of RLIM increases TRF1 levels and leads to telomere shortening. Co-immunoprecipitation, shRNA knockdown, overexpression, telomere length assays, proteasome inhibitor experiments The Journal of biological chemistry Medium 19164295
2010 Maternal RLIM deposited in oocytes is required for imprinted X chromosome inactivation (iXCI) in mice; conditional knockout of Rnf12 in oocytes causes lethality in female embryos due to failure of Xist cloud formation and paternal X silencing, while RLIM is dispensable for random XCI in embryonic stem cells. Conditional oocyte-specific knockout mouse genetics, Xist RNA FISH, X-linked gene expression analysis Nature High 20962847
2011 RNF12 acts in trans to activate Xist transcription and is essential for initiation of random XCI; Rnf12-/- female ES cells fail to initiate XCI, and RNF12 regulation does not operate through Tsix or Xist intron 1. Rnf12 knockout ES cell differentiation, Xist RNA FISH, gene expression analysis PLoS genetics High 21298085
2011 Rnf12 expression in mouse ES cells is negatively regulated by the pluripotency transcription factors Nanog, Oct4, and Sox2, linking the XCI activator to the pluripotency network. Chromatin immunoprecipitation, reporter assays, factor knockdown/overexpression in ES cells Human genetics Medium 21544581
2012 RNF12 directly ubiquitinates the pluripotency factor REX1, triggering its proteasomal degradation; REX1 binds Xist and Tsix regulatory regions and inhibits Xist transcription, so RNF12-mediated REX1 breakdown initiates XCI in a dose-dependent manner. Co-immunoprecipitation, in vitro ubiquitination assay, ChIP-seq, Rnf12-KO ES cells, Rex1 overexpression/knockdown, Xist RNA FISH Nature High 22596162
2012 RNF12 specifically binds Smad7 and induces its polyubiquitination and proteasomal degradation, thereby potentiating TGF-β/BMP/Nodal–Smad signaling; RNF12-deficient mouse ES cells show elevated Smad7 and attenuated TGF-β responses. Co-immunoprecipitation, in vitro ubiquitination assay, RNF12 KO ES cells, zebrafish gain/loss-of-function, rescue experiments Molecular cell High 22560923
2012 Paternal Rnf12/RLIM expressed in mammary glands is a critical survival factor for milk-producing alveolar cells; knockout of Rnf12 in mammary glands inhibits alveolar differentiation and causes apoptosis of differentiating alveolar cells, mediated by the paternal allele due to nonrandom maternal XCI in mammary epithelial cells. Conditional mammary gland knockout, pregnancy/lactation phenotyping, apoptosis assays, genetic complementation Cell High 22541433
2013 RLIM/Rnf12 protein shuttles between nucleus and cytoplasm, regulated by phosphorylation of serine S214 within its nuclear localization sequence; blocking this shuttling (by expressing nuclear- or cytoplasmic-locked RLIM) inhibits alveolar cell survival activity. Phosphomimetic/phosphoresistant mutagenesis, subcellular fractionation, live-cell imaging, mammary alveolar cell survival assays Molecular biology of the cell High 23904271
2014 RNF12 acts as a trans-acting, dose-dependent XCI activator that operates in concert with cis-regulatory elements (Jpx, Ftx, Xpr region) to activate Xist and overcome Tsix repression; RNF12 functions at two sequential steps: two active Rnf12 copies drive XCI initiation, and one copy must remain active for Xi establishment. X-pairing deletion ES cells, transgenic Rnf12 copy-number variation, Xist RNA FISH, genetic epistasis Molecular cell High 24613346
2014 RLIM is dispensable for random XCI in the mouse embryonic epiblast; female cells lacking RLIM from pre-implantation stages still form Xist clouds and H3K27me3 foci and have full embryogenic potential, and RLIM levels are downregulated in cells undergoing rXCI. Mouse genetics (early conditional KO), Xist FISH, H3K27me3 immunostaining, western blot quantification Nature High 24870238
2018 RNF12 XLID patient mutations specifically impair E3 ubiquitin ligase catalytic activity by either inactivating the RING domain or disrupting a distal regulatory region required for efficient ubiquitin transfer, thereby impairing ubiquitylation of developmentally relevant substrates (REX1, SMAD7) and disrupting stem cell maintenance and neural differentiation. In vitro ubiquitination assay with XLID mutants, ES cell differentiation, neural differentiation assays, site-directed mutagenesis Cell reports High 29742418
2018 Loss of Rex1 rescues the rXCI phenotype in Rnf12-/- ES cells, and genetic ablation of Rex1 in Rnf12-/- mice rescues the iXCI phenotype, yielding viable fertile females with normal XCI; this establishes REX1 as the critical in vivo target of RNF12 in XCI. Double-knockout mouse genetics (Rnf12-/-:Rex1-/-), iXCI and rXCI phenotyping, Xist RNA FISH Nature communications High 30420655
2018 RNF12 physically interacts with BRF1 (a TFIIIB subunit) and catalyzes Lys27- and Lys33-linked polyubiquitination of BRF1, negatively regulating RNA polymerase III-dependent transcription and cell proliferation. Co-immunoprecipitation, in vitro ubiquitination assay with linkage-specific analysis, Pol III transcription assays, cell proliferation assays The Journal of biological chemistry Medium 30413534
2020 TRIM28 regulates RLIM protein levels and, through RLIM and MDM2, modulates p53 levels during lung tumorigenesis, placing RLIM in a sequential ubiquitination cascade: TRIM28→RLIM→MDM2→p53. Co-immunoprecipitation, overexpression/knockdown in lung cancer cells, xenograft models, western blot Cell death and differentiation Medium 33328571
2016 RLIM associates with c-Myc in vivo and in vitro and promotes its polyubiquitination independently of Ser62/Thr58 phosphorylation; however, RLIM-mediated ubiquitination does not affect c-Myc stability but instead inhibits its transcriptional activity, restraining cell proliferation. Co-immunoprecipitation, in vivo ubiquitination assay, transcriptional reporter assays, cell proliferation assays PloS one Medium 27684546
2016 RNF12 interacts with MDM2, targets it for ubiquitination and proteasomal degradation (independently of MDM2's self-ubiquitination), thereby elevating p53 levels and promoting p53-dependent cell growth suppression and apoptosis. Yeast two-hybrid, co-immunoprecipitation, in vivo ubiquitination assay, p53 reporter assays, apoptosis assays Cancer letters Medium 26926424
2021 Rlim is highly expressed in post-meiotic round spermatids and Sertoli cells in mouse testis; systemic and spermatogenic-lineage-specific Rlim knockout results in lower numbers of mature sperm with excess cytoplasm, decreased sperm motility, and reduced in vitro fertilization rates, revealing a role for Rlim in spermiogenesis. Systemic and conditional (spermatogenic cell-specific) Rlim knockout mice, sperm morphology, motility, and IVF assays, immunofluorescence eLife High 33620316
2022 RNF12 relieves REX1-mediated repression of Usp26, increasing USP26 abundance; USP26 then forms complexes with RNF12 and prevents RNF12 autoubiquitylation and degradation, establishing a feed-forward amplification loop that is required for germ cell differentiation and is disrupted by TOKAS and infertility-associated variants. Global quantitative proteomics, Co-IP, ubiquitination assays, Usp26 reporter assays, germ cell differentiation in vitro, patient variant functional testing Science signaling High 35857630
2022 AKT phosphorylates RNF12, inducing its nuclear localization and maintaining its stability, which accelerates SMAD7 degradation and enhances TGF-β-driven breast cancer metastasis; RNF12 and AKT cooperate functionally in cancer cell migration. Co-immunoprecipitation, phosphorylation assays, nuclear/cytoplasmic fractionation, migration/invasion assays, zebrafish and murine xenograft metastasis models Cell death & disease Medium 35013159
2022 RLIM ubiquitinates ZC4H2 (stabilizing it rather than targeting it for degradation), which in turn stabilizes RNF220, forming an RLIM–ZC4H2–RNF220 cascade required for full activation of Sonic hedgehog signaling in cerebellar granule neuron progenitors and medulloblastoma progression. Co-immunoprecipitation, ubiquitination assays, Shh signaling reporter assays, knockdown/overexpression in cerebellar cells Journal of molecular cell biology Medium 35040952
2024 RNF12 is recruited to specific genomic locations via a consensus sequence motif in a non-catalytic basic region, enabling co-localization with REX1 at gene promoters; this chromatin targeting requires an N-terminal autoinhibitory mechanism and is critical for REX1 ubiquitylation and downstream gene regulation. ChIP-seq, proximity-labeling proteomics (BioID), mutagenesis of basic region, in vitro ubiquitination assay, gene expression analysis Life science alliance High 38199845
2023 The Rlim–Rex1 axis is active in pre-implantation mouse embryos for iXCI regulation; upon implantation, Rex1 levels are downregulated independently of Rlim specifically in epiblast cells, explaining why Rlim is required for iXCI but not rXCI. Mouse genetics, immunofluorescence for Rex1 in blastocyst compartments, Rlim conditional KO embryo analysis Proceedings of the National Academy of Sciences of the United States of America High 38113263
2020 KSHV LANA protein interacts with RLIM and promotes RLIM autoubiquitination and proteasomal degradation; LANA differentially modulates degradation of RLIM substrates, enhancing degradation of LDB1 and LMO2 but preventing RLIM-mediated degradation of LHX3 and TRF1. Co-immunoprecipitation (with proteasome inhibitor MG132), RING finger mutant RLIM resistance assay, western blot, transcriptional assays Journal of virology Medium 31801865
2017 RLIM directly binds MIZ1, disrupting the interaction between c-MYC and MIZ1, and enhancing p15 and p21 transcription, thereby suppressing hepatocellular carcinoma cell proliferation. Co-immunoprecipitation, chromatin immunoprecipitation, cell cycle and proliferation assays, overexpression experiments Oncotarget Medium 29137325
2014 RLIM directly interacts with Stathmin and promotes its ubiquitin-dependent proteasomal degradation; depletion of endogenous RLIM by siRNA increases Stathmin protein levels, leading to altered cell proliferation and cell cycle progression in osteosarcoma cells. Co-immunoprecipitation, siRNA knockdown, overexpression, proteasome inhibitor experiments, cell cycle analysis Cellular signalling Medium 24686088
2025 Rlim in GABAergic neurons of the suprachiasmatic nucleus (SCN) regulates diurnal energy homeostasis: Rlim in RIP-Cre+ neurons governs daily thermogenic rhythms in brown adipose tissue, while Rlim in VIP-expressing neurons modulates diurnal feeding behavior; Rlim KO mice are lean and resistant to diet-induced obesity. Systemic and cell-type-specific conditional Rlim knockout mice, metabolic phenotyping, BAT thermogenesis measurements, feeding behavior monitoring bioRxivpreprint Medium 40766619
2009 CLIM and RLIM function as ERα cofactors in breast cancer cells; RLIM co-localizes and interacts with ERα, associates with estrogen-responsive promoters, and enhances transcriptional activation of endogenous ERα target genes—opposing its inhibitory role on LIM-HD transcription factors. Co-immunoprecipitation from breast tumor tissue, chromatin immunoprecipitation on endogenous target promoters, siRNA knockdown, reporter assays Cancer research Medium 19117995
2018 Rnf12 is necessary for initiation of retinal gliogenesis in the mouse retina; it acts as a negative regulator of LDB1, and its loss prevents the developmental decrease in the LHX2-LDB1 complex that normally accompanies gliogenesis onset. In vivo conditional retinal Rnf12 knockout, retinal cell fate analysis, immunostaining for LHX2/LDB1 complex Development (Cambridge, England) Medium 29650591
2024 RLIM ubiquitinates PML (promyelocytic leukemia protein) and promotes its degradation; AKT phosphorylation of RLIM stabilizes it and enhances RLIM-mediated PML degradation, enabling colon cancer cell growth and metastasis promoted by CAF-secreted COMP. Co-immunoprecipitation, ubiquitination assays, phosphorylation assays, overexpression/knockdown, in vivo xenograft and metastasis models Journal of gastroenterology and hepatology Medium 39162054

Source papers

Stage 0 corpus · 57 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 RNF12 is an X-Encoded dose-dependent activator of X chromosome inactivation. Cell 188 19945382
2012 RNF12 initiates X-chromosome inactivation by targeting REX1 for degradation. Nature 165 22596162
2010 Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice. Nature 138 20962847
1999 RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex. Nature genetics 128 10431247
2011 RNF12 activates Xist and is essential for X chromosome inactivation. PLoS genetics 119 21298085
2012 RNF12 controls embryonic stem cell fate and morphogenesis in zebrafish embryos by targeting Smad7 for degradation. Molecular cell 80 22560923
2014 The trans-activator RNF12 and cis-acting elements effectuate X chromosome inactivation independent of X-pairing. Molecular cell 59 24613346
2020 Sequential ubiquitination of p53 by TRIM28, RLIM, and MDM2 in lung tumorigenesis. Cell death and differentiation 54 33328571
2014 RLIM is dispensable for X-chromosome inactivation in the mouse embryonic epiblast. Nature 52 24870238
2009 Regulation of estrogen-dependent transcription by the LIM cofactors CLIM and RLIM in breast cancer. Cancer research 52 19117995
2011 The X-inactivation trans-activator Rnf12 is negatively regulated by pluripotency factors in embryonic stem cells. Human genetics 48 21544581
2009 Ubiquitin Ligase RLIM Modulates Telomere Length Homeostasis through a Proteolysis of TRF1. The Journal of biological chemistry 48 19164295
2018 RNF12 X-Linked Intellectual Disability Mutations Disrupt E3 Ligase Activity and Neural Differentiation. Cell reports 32 29742418
2018 REX1 is the critical target of RNF12 in imprinted X chromosome inactivation in mice. Nature communications 31 30420655
2018 Pathogenic variants in E3 ubiquitin ligase RLIM/RNF12 lead to a syndromic X-linked intellectual disability and behavior disorder. Molecular psychiatry 27 29728705
2015 Syndromic X-linked intellectual disability segregating with a missense variant in RLIM. European journal of human genetics : EJHG 27 25735484
2012 Paternal RLIM/Rnf12 is a survival factor for milk-producing alveolar cells. Cell 26 22541433
2000 Functional characterization of the gene encoding RLIM, the corepressor of LIM homeodomain factors. Genomics 26 11013082
2018 Ldb1- and Rnf12-dependent regulation of Lhx2 controls the relative balance between neurogenesis and gliogenesis in the retina. Development (Cambridge, England) 24 29650591
2013 Functional activity of RLIM/Rnf12 is regulated by phosphorylation-dependent nucleocytoplasmic shuttling. Molecular biology of the cell 24 23904271
2014 Rlim, an E3 ubiquitin ligase, influences the stability of Stathmin protein in human osteosarcoma cells. Cellular signalling 20 24686088
2011 RLIM interacts with Smurf2 and promotes TGF-β induced U2OS cell migration. Biochemical and biophysical research communications 20 21945933
2022 RNF12 is regulated by AKT phosphorylation and promotes TGF-β driven breast cancer metastasis. Cell death & disease 19 35013159
2016 E3 Ubiquitin Ligase RLIM Negatively Regulates c-Myc Transcriptional Activity and Restrains Cell Proliferation. PloS one 18 27684546
2015 PIWIL1 destabilizes microtubule by suppressing phosphorylation at Ser16 and RLIM-mediated degradation of Stathmin1. Oncotarget 17 26317901
2017 Rlim-Dependent and -Independent Pathways for X Chromosome Inactivation in Female ESCs. Cell reports 16 29281819
2016 RNF12 promotes p53-dependent cell growth suppression and apoptosis by targeting MDM2 for destruction. Cancer letters 16 26926424
2021 Deficient spermiogenesis in mice lacking Rlim. eLife 14 33620316
2019 Rlim/Rnf12, Rex1, and X Chromosome Inactivation. Frontiers in cell and developmental biology 12 31737626
2021 A novel RLIM/RNF12 variant disrupts protein stability and function to cause severe Tonne-Kalscheuer syndrome. Scientific reports 11 33953269
1994 Distribution of Rlim, an LIM homeodomain gene, in the rat brain. Neuroscience letters 11 7914684
2022 Sequential stabilization of RNF220 by RLIM and ZC4H2 during cerebellum development and Shh-group medulloblastoma progression. Journal of molecular cell biology 10 35040952
2018 RNF12 catalyzes BRF1 ubiquitination and regulates RNA polymerase III-dependent transcription. The Journal of biological chemistry 10 30413534
2016 Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice. PLoS genetics 10 27788132
2020 Kaposi's Sarcoma-Associated Herpesvirus LANA Modulates the Stability of the E3 Ubiquitin Ligase RLIM. Journal of virology 8 31801865
2020 RLIM Is a Candidate Dosage-Sensitive Gene for Individuals with Varying Duplications of Xq13, Intellectual Disability, and Distinct Facial Features. American journal of human genetics 8 33159883
2022 An RNF12-USP26 amplification loop drives germ cell specification and is disrupted by disease-associated mutations. Science signaling 7 35857630
2021 RNF12 Promotes Glioblastoma Malignant Proliferation via Destructing RB1 and Regulating MAPK Pathway. Journal of healthcare engineering 7 34900190
2013 p53 Represses transcription of RING finger LIM domain-binding protein RLIM through Sp1. PloS one 7 23650532
2019 TUG1 promotes the development of prostate cancer by regulating RLIM. European review for medical and pharmacological sciences 6 30915735
2001 Expression and regulation of the LIM-class homeobox gene rlim-1 in neuronal progenitors of the rat cerebellum. Journal of neuroscience research 6 11170173
2024 Cancer-associated fibroblasts promote the proliferation and metastasis of colon cancer by mediating the RLIM/PML axis through paracrine COMP. Journal of gastroenterology and hepatology 5 39162054
2023 Roles of the Rlim-Rex1 axis during X chromosome inactivation in mice. Proceedings of the National Academy of Sciences of the United States of America 5 38113263
2012 Inhibiting the inhibitor: the role of RNF12 in TGF-β superfamily signaling. Molecular cell 5 22681885
2019 A novel approach to differentiate rat embryonic stem cells in vitro reveals a role for RNF12 in activation of X chromosome inactivation. Scientific reports 4 30988473
2017 RLIM suppresses hepatocellular carcinogenesis by up-regulating p15 and p21. Oncotarget 3 29137325
2012 Releasing the break on X chromosome inactivation: Rnf12/RLIM targets REX1 for degradation. Cell research 3 22785560
2024 Chromatin targeting of the RNF12/RLIM E3 ubiquitin ligase controls transcriptional responses. Life science alliance 2 38199845
2024 RLIM-specific activity reporters define variant pathogenicity in Tonne-Kalscheuer syndrome. HGG advances 2 39482882
1996 Localization of mRNAs for Rlim-1, the rat Xlim-1 homolog, in the developing rat brain. Brain research. Molecular brain research 2 9011751
2024 How does the Xist activator Rlim/Rnf12 regulate Xist expression? Biochemical Society transactions 1 38747697
2023 Knockout of Rlim Results in a Sex Ratio Shift toward Males but Superovulation Cannot Compensate for the Reduced Litter Size. Animals : an open access journal from MDPI 1 36978620
2021 Knockdown of RLIM inhibits XIST expression and improves developmental competence of cloned male pig embryos. Molecular reproduction and development 1 33650239
2026 The RING E3 ligase RLIM drives oxidative stress-induced stem cell dysfunction through MDM2-p53 signaling. The Journal of biological chemistry 0 41866032
2025 Rlim coordinates diurnal regulation of food intake and thermogenesis. bioRxiv : the preprint server for biology 0 40766619
2025 A novel missense variant at the site of interaction between RLIM and E2 ubiquitin-conjugating enzymes causes Tønne-Kalscheuer syndrome. BMC pediatrics 0 41068697
2023 Retracted: RNF12 Promotes Glioblastoma Malignant Proliferation via Destructing RB1 and Regulating MAPK Pathway. Journal of healthcare engineering 0 38094843