Affinage

MYLIP

E3 ubiquitin-protein ligase MYLIP · UniProt Q8WY64

Length
445 aa
Mass
49.9 kDa
Annotated
2026-04-29
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MYLIP (also called IDOL) is an E3 ubiquitin ligase that controls the abundance of LDL receptor family members at the plasma membrane, thereby regulating cholesterol uptake, Reelin signaling, and systemic energy balance. Transcriptionally induced by LXR, MYLIP binds LDLR, VLDLR, and ApoER2 through its FERM domain and catalyzes Lys-63-linked ubiquitination of their cytoplasmic tails via its RING domain in partnership with the E2 enzyme UBE2D, routing these receptors through an epsin- and ESCRT-dependent, clathrin-independent pathway to lysosomes for degradation (PMID:19520913, PMID:20427281, PMID:21734303, PMID:21685362, PMID:23382078). MYLIP protein stability is enhanced by SUMO1 conjugation at K293, which antagonizes autoubiquitination, while the deubiquitinase USP2 forms a tripartite complex with MYLIP and LDLR to deubiquitinate LDLR and restrain its degradation (PMID:33154164, PMID:26666640). In neurons, MYLIP-dependent turnover of ApoER2 and VLDLR governs dendritic spine plasticity, long-term potentiation, and experience-dependent circuit remodeling, and hypothalamic MYLIP control of VLDLR abundance regulates food intake, thermogenesis, and susceptibility to diet-induced obesity (PMID:28891791, PMID:32072135).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2009 High

    Identification of MYLIP/IDOL as an LXR-inducible E3 ligase that ubiquitinates LDLR and promotes its degradation established the first sterol-regulated, post-translational pathway for LDLR turnover independent of PCSK9.

    Evidence Co-IP/ubiquitination assays, siRNA, adenoviral overexpression in mouse liver, LXR-knockout mice

    PMID:19520913

    Open questions at the time
    • Catalytic domain requirements and E2 partner not yet defined
    • Substrate specificity beyond LDLR unknown
    • Endocytic route not characterized
  2. 2010 High

    Extension of IDOL substrate scope to VLDLR and ApoER2 linked the LXR-IDOL axis to Reelin signaling and revealed IDOL as a general regulator of the LDLR family, while statin treatment was shown to suppress IDOL transcription, adding a pharmacological dimension.

    Evidence Ubiquitination assays, LXR agonist in vivo, Dab1 phosphorylation readout; qRT-PCR and siRNA in hepatocytes

    PMID:20427281 PMID:21069265

    Open questions at the time
    • Domain architecture mediating receptor recognition unresolved
    • Whether Reelin signaling feeds back on IDOL unknown
  3. 2011 High

    Structural and biochemical dissection of IDOL's FERM and RING domains, identification of UBE2D as the obligate E2 partner (crystal structure at 2.1 Å), and demonstration that RING-mediated dimerization is required for activity defined the minimal catalytic mechanism.

    Evidence X-ray crystallography, NMR, in vitro ubiquitination, domain mutagenesis, fluorescence co-localization

    PMID:21685362 PMID:21734303

    Open questions at the time
    • Full-length IDOL structure unavailable
    • Whether other E2s can substitute in vivo untested
    • Structural basis of FERM–receptor interaction not resolved at atomic level
  4. 2011 High

    The MYLIP N342S coding polymorphism was linked to total cholesterol variation in humans and shown to alter LDLR targeting efficiency without affecting intrinsic E3 activity, providing the first human genetic evidence that IDOL variation affects lipid metabolism.

    Evidence Population genetic fine-mapping in Mexican cohort, cell-based LDLR degradation and LDL uptake assays with site-directed mutagenesis

    PMID:21765216

    Open questions at the time
    • Structural mechanism by which N342S alters receptor targeting unclear
    • Replication in diverse populations incomplete at that time
  5. 2013 High

    Elucidation of the IDOL-triggered endocytic itinerary showed that LDLR is internalized via a clathrin-, caveolin-, and dynamin-independent route that depends on epsin and the ESCRT machinery, with USP8 acting as a downstream deubiquitinase required for MVB sorting.

    Evidence Single-particle tracking, electron microscopy, siRNA of ESCRT-0/I components and epsin, lipid raft fractionation

    PMID:23382078 PMID:23733886

    Open questions at the time
    • Identity of the cargo adaptor linking ubiquitinated LDLR to epsin not defined
    • Whether the same route applies to VLDLR/ApoER2 not tested
  6. 2013 Medium

    Reelin was found to upregulate IDOL in hippocampal neurons to decrease VLDLR, establishing a neuronal activity–IDOL feedback loop that modulates Reelin receptor availability.

    Evidence shRNA knockdown of IDOL in primary hippocampal neurons, Western blot for VLDLR

    PMID:23990472

    Open questions at the time
    • Signaling pathway from Reelin to IDOL transcription not mapped
    • Whether LXR mediates this induction in neurons unresolved
    • Single-lab finding
  7. 2014 High

    Species- and tissue-specificity of the LXR–IDOL axis was resolved: in mice IDOL operates peripherally but not in liver, whereas in primates hepatic IDOL is LXR-responsive and its knockdown prevents LXR-driven LDL elevation, clarifying why murine models underestimate IDOL's role in cholesterol homeostasis.

    Evidence Idol-KO mice, antisense oligonucleotide knockdown in cynomolgus monkeys, plasma lipid profiling

    PMID:25440061

    Open questions at the time
    • Molecular basis for species-specific hepatic LXR–IDOL regulation unknown
    • Whether IDOL ASO is therapeutically viable long-term not assessed
  8. 2014 High

    Gain-of-function expression of a stabilized IDOL in mouse liver was sufficient to cause hypercholesterolemia and atherosclerosis, establishing IDOL as a causal driver of cardiovascular disease when overactive.

    Evidence Albumin-promoter transgenic mice, Western diet, atherosclerotic lesion quantification

    PMID:24935961

    Open questions at the time
    • Whether endogenous IDOL levels ever reach pathological thresholds in humans unclear
    • Contribution of non-LDLR substrates to atherosclerosis phenotype not dissected
  9. 2015 High

    Discovery of USP2 as a deubiquitinase that forms a tripartite complex with IDOL and LDLR revealed a paradoxical regulatory circuit: USP2 stabilizes IDOL yet attenuates LDLR degradation by deubiquitinating LDLR directly.

    Evidence Genetic screen, reciprocal Co-IP, in vitro deubiquitylation, siRNA, LDL uptake assay

    PMID:26666640

    Open questions at the time
    • In vivo relevance in animal models not demonstrated
    • Whether USP2 competes with USP8 at the ESCRT step unknown
  10. 2017 High

    IDOL was shown to be essential for activity-dependent regulation of synaptic ApoER2, dendritic spine remodeling, LTP, and experience-dependent cortical plasticity, establishing a non-metabolic, neuronal function.

    Evidence Neuronal conditional KO mice, hippocampal slice LTP, spine imaging, barrel cortex mapping, behavioral learning assays

    PMID:28891791

    Open questions at the time
    • Whether LDLR or VLDLR also contributes to the synaptic phenotype not fully excluded
    • Upstream signals regulating neuronal IDOL during plasticity not identified
  11. 2019 High

    Systematic tissue-specific knockout and scRNA-seq identified neuronal VLDLR (not hepatic LDLR) as the primary IDOL substrate governing systemic energy balance, linking hypothalamic IDOL to food intake, thermogenesis, and diet-induced obesity.

    Evidence Conditional KO in six tissue compartments, hypothalamic single-cell RNA-seq, metabolic phenotyping

    PMID:32072135

    Open questions at the time
    • Specific hypothalamic neuronal subtype(s) mediating the effect not pinpointed
    • Whether ApoER2 contributes to hypothalamic energy regulation via IDOL untested
  12. 2020 High

    SUMOylation at K293 was identified as a stabilizing post-translational modification of IDOL that antagonizes autoubiquitination; SENP1-mediated deSUMOylation destabilizes IDOL and consequently increases LDLR, adding a SUMO-dependent regulatory layer.

    Evidence SUMOylation assay, K293 mutagenesis, SENP1 overexpression/knockdown, LDLR and LDL uptake measurement

    PMID:33154164

    Open questions at the time
    • Physiological signals controlling IDOL SUMOylation unknown
    • Whether other SUMO sites exist not exhaustively mapped
    • Interplay between SUMOylation and USP2-mediated regulation unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length atomic structure of IDOL, the structural basis of FERM domain–receptor selectivity, the signaling pathways that regulate neuronal IDOL during synaptic plasticity, and whether therapeutic IDOL inhibition can safely lower LDL cholesterol in primates without perturbing neuronal or metabolic functions.
  • No full-length IDOL structure
  • No selective small-molecule IDOL inhibitor reported
  • Crosstalk between SUMO, USP2, and epsin/ESCRT pathways not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016874 ligase activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 2 GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 7 R-HSA-162582 Signal Transduction 4 R-HSA-382551 Transport of small molecules 4 R-HSA-5653656 Vesicle-mediated transport 2
Partners
LDLRLRP8SENP1UBE2D1USP2USP8VLDLR

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 IDOL (MYLIP) is an E3 ubiquitin ligase transcriptionally induced by LXR that triggers ubiquitination of the LDLR on its cytoplasmic domain, targeting it for degradation, thereby suppressing LDL uptake. LXR ligand reduces LDLR protein levels in vivo; Idol knockdown increases LDLR protein and promotes LDL uptake; adenoviral Idol expression in mouse liver promotes LDLR degradation and elevates plasma LDL levels. Co-IP/ubiquitination assay, siRNA knockdown, adenoviral overexpression in vivo, LXR knockout mice Science High 19520913
2010 IDOL also targets VLDLR and ApoER2 (in addition to LDLR), triggering ubiquitination of their cytoplasmic tails and lysosomal degradation. LXR activation in mice increases Idol expression and decreases Vldlr levels in vivo. IDOL-dependent reduction of VLDLR decreases Reelin binding and Dab1 phosphorylation, linking LXR-IDOL to Reelin signaling. Ubiquitination assays, siRNA knockdown, LXR agonist treatment in vivo, Dab1 phosphorylation assay The Journal of biological chemistry High 20427281
2011 IDOL contains conserved FERM and RING domains both required for LDLR degradation. The RING domain promotes ubiquitination in vitro and Lys-63-specific LDLR ubiquitination in vivo. The FERM domain binds the LDLR and co-localizes with it at the plasma membrane; a phosphotyrosine-binding element in the FERM domain and residues in the LDLR preceding the NPVY endocytosis motif are critical for degradation. In vitro ubiquitination assay, domain mutagenesis, fluorescence co-localization, homology modeling The Journal of biological chemistry High 21734303
2011 IDOL forms a complex with the E2 ubiquitin-conjugating enzyme UBE2D family (UBE2D1-4). NMR chemical shift mapping and a 2.1 Å crystal structure of the IDOL RING domain–UBE2D1 complex revealed the structural basis for E2 selectivity. Mutations disrupting IDOL dimerization or IDOL–UBE2D interaction block IDOL-dependent LDLR ubiquitination and degradation; dominant-negative UBE2D inhibits IDOL-mediated LDLR degradation in cells. Cell-free ubiquitination assay, NMR chemical shift mapping, X-ray crystallography (2.1 Å), structure-guided mutagenesis, dominant-negative expression Genes & development High 21685362
2011 The MYLIP N342S polymorphism (rs9370867) is associated with high total cholesterol in a Mexican population. Functional characterization showed that the Asn-encoding allele supports more potent LDLR degradation and decreased LDL uptake; mutagenesis of residue 342 does not affect intrinsic E3 ligase activity but is critical for LDLR targeting. Population genetics fine-mapping, cell-based LDLR degradation assay, site-directed mutagenesis, LDL uptake assay The Journal of clinical investigation High 21765216
2012 FGF21 reduces MYLIP/IDOL at the RNA and protein level and increases LDLR levels and stability. FGF21 also enhances expression of Canopy2/Msap, which interacts with MYLIP/IDOL. Cnpy2/Msap knockdown abolishes the FGF21 effect on LDLR levels, and FGF21 increases LDL particle uptake additively with statins. siRNA knockdown, Western blot, DiI-LDL uptake assay, overexpression in hepatocyte and macrophage cells The Journal of biological chemistry Medium 22378787
2013 IDOL stimulates clathrin-independent, caveolae-independent endocytosis of the LDLR. IDOL is recruited to the plasma membrane by LDLR and facilitates LDLR entry into the multivesicular body (MVB)/ESCRT pathway for lysosomal degradation. siRNA knockdown of ESCRT-0 (HGS) or ESCRT-I (TSG101) prevents IDOL-mediated LDLR degradation. USP8 deubiquitinates LDLR downstream of IDOL and is required for LDLR entry into the MVB pathway. Real-time single-particle tracking, electron microscopy, siRNA knockdown of ESCRT components, live-cell imaging Molecular and cellular biology High 23382078
2013 IDOL-dependent LDLR internalization is clathrin-, caveolin-, macroautophagy-, and dynamin-independent, targeting a LDLR pool in lipid rafts. It depends on the endocytic protein epsin, and degradation can be blocked by perturbation of ESCRT or by USP8. Pharmacological and genetic inhibition of endocytic pathways, lipid raft fractionation, LDL uptake assay Journal of lipid research High 23733886
2013 Reelin decreases VLDLR levels in hippocampal neurons via upregulation of the E3 ligase Mylip/IDOL; shRNA knockdown of Mylip/IDOL abrogates the Reelin-induced decrease in VLDLRs. BDNF increases VLDLR levels by increasing gene expression, acting through a transcriptional mechanism. shRNA knockdown, Western blot, primary hippocampal neuron culture The Journal of biological chemistry Medium 23990472
2014 The LXR-IDOL axis is tissue- and species-specific. In mice, LXR agonist induces Idol in peripheral tissues but not liver, and does not raise plasma LDL; Idol-deficient mice have elevated LDLR in peripheral but not hepatic tissues. In cynomolgus monkeys, LXR activation induces hepatic IDOL, reduces hepatic LDLR protein, and raises plasma LDL; antisense oligonucleotide knockdown of IDOL in monkeys blunts LXR-induced LDL elevation. Idol knockout mice, antisense oligonucleotide knockdown in nonhuman primates, plasma lipid measurement, tissue LDLR protein quantification Cell metabolism High 25440061
2014 Liver-specific expression of a degradation-resistant, dominant-active IDOL (sIDOL) in mice dramatically reduces hepatic LDLR protein, elevates plasma LDL cholesterol on chow and Western diet, and causes marked atherosclerotic lesion formation, demonstrating that increased hepatic IDOL activity is sufficient to cause hypercholesterolemia and atherosclerosis. Albumin-promoter transgenic mice, Western diet feeding, atherosclerosis lesion quantification, plasma lipid measurement Circulation research High 24935961
2015 USP2 (both isoforms USP2-69 and USP2-45) interacts with IDOL, promotes its deubiquitylation in an activity-dependent manner, and paradoxically stabilizes IDOL while attenuating IDOL-mediated LDLR degradation. A tripartite IDOL–USP2–LDLR complex was identified in which USP2 deubiquitylates LDLR and prevents its degradation. Loss of USP2 reduces LDLR in an IDOL-dependent manner. Genetic screen, reciprocal Co-IP, deubiquitylation assay, siRNA knockdown, LDL uptake assay Circulation research High 26666640
2015 MARCH6 indirectly regulates LDLR levels by inducing IDOL expression. Loss of MARCH6 increases SREBP-regulated gene expression but decreases cellular lipoprotein uptake due to enhanced lysosomal LDLR degradation driven by IDOL induction. Genetic knockdown/knockout, SREBP reporter, LDLR protein measurement, LDL uptake assay Molecular and cellular biology Medium 26527619
2015 DUB inhibition transcriptionally induces IDOL expression through an LXR-independent mechanism mediated by a 70-bp proximal promoter region distinct from the LXR-responsive element, leading to LDLR ubiquitylation and lysosomal degradation. Pharmacological DUB inhibition, promoter deletion analysis, Lxrαβ−/− MEFs, LDLR protein/mRNA measurement The Journal of biological chemistry Medium 26719329
2017 IDOL determines synaptic ApoER2 protein levels in response to neuronal activation and regulates dendritic spine morphogenesis and plasticity. Loss of IDOL in neurons causes constitutive ApoER2 overexpression, impairs activity-dependent structural remodeling of spines, and produces defective LTP. IDOL-deficient mice show impaired experience-dependent reorganization of barrel cortex synaptic circuits and diminished spatial and associative learning. Neuronal IDOL knockout, LTP recording in hippocampal slices, dendritic spine imaging, barrel cortex mapping, behavioral learning assays eLife High 28891791
2018 Deletion of Idol in mice protects from diet-induced obesity and metabolic dysfunction, reducing circulating cholesterol, triglycerides, glucose, and insulin. Idol-KO mice show protection from weight gain, reduced hepatosteatosis, increased UCP1/TH in brown adipose tissue, and increased locomotion and lipoprotein particle clearance. Idol knockout mice, Western diet feeding, indirect calorimetry, tissue gene expression, in vivo lipoprotein clearance Arteriosclerosis, thrombosis, and vascular biology High 29903737
2019 IDOL controls systemic energy balance through regulation of VLDLR (not LDLR) abundance in neurons, not in peripheral metabolic tissues. Tissue-specific knockout analysis showed that neuronal IDOL deletion alters hypothalamic gene expression linked to metabolic control. VLDLR is identified as the primary mediator of IDOL effects on food intake, thermogenesis, and diet-induced obesity. Tissue-specific (neuron, liver, adipose, endothelium, intestine, skeletal muscle) conditional KO mice, single-cell RNA sequencing of hypothalamus, metabolic phenotyping Nature metabolism High 32072135
2020 IDOL is SUMOylated at least at K293 by SUMO1. SUMOylation counteracts IDOL autoubiquitination at K293, stabilizing IDOL protein and increasing its levels. SENP1 reverses SUMOylation of IDOL in an activity-dependent manner, thereby decreasing IDOL levels, increasing LDLR protein, and enhancing LDL uptake. Loss of SENP1 lowers LDLR in an IDOL-dependent manner. SUMOylation assay, site-directed mutagenesis (K293), SENP1 overexpression and siRNA knockdown, LDLR protein measurement, LDL endocytosis assay The Journal of biological chemistry High 33154164
2010 Statin treatment rapidly and dose-dependently decreases Idol mRNA in human hepatoma cells and primary hepatocytes, in contrast to its induction of PCSK9. Idol siRNA transfection increases basal LDLR protein by ~60% in HepG2 cells, and the statin-induced increase in LDLR is partially dependent on Idol suppression. siRNA knockdown, qRT-PCR, Western blot in hepatocyte cell lines and primary hepatocytes International journal of molecular medicine Medium 21069265
2012 LXR agonist treatment of HCV-infected Huh7.5.1 cells inhibits HCV infection in a dose-dependent manner; exogenous expression of Idol confers resistance to HCV infection. This defines an LXR-IDOL-LDLR pathway relevant to HCV entry, as LDLR is required for HCV particle entry. Adenoviral IDOL overexpression, LXR agonist treatment, HCV infection assay in Huh7.5.1 cells Antiviral research Medium 22713431
2020 miR-224 and miR-520d directly repress IDOL (as well as PCSK9 and HMGCR) through their 3'-UTR response elements. Overexpression of miR-224 or miR-520d in hepatocytes reduces IDOL mRNA and protein, leading to increased LDLR protein and cell-surface expression and enhanced LDL binding. In vivo delivery of miR-224 to Ldlr+/- mice decreases plasma LDL cholesterol by 15%. 3'-UTR luciferase reporter assays with response element mutagenesis, gain/loss-of-function in hepatocytes, in vivo lipid nanoparticle delivery in mice Frontiers in cardiovascular medicine Medium 32528976
2020 Platycodin D reduces IDOL mRNA, decreasing IDOL-mediated LDLR ubiquitination, increasing LDLR protein half-life (cycloheximide chase), and enhancing LDL-C uptake in HepG2 cells; effects are synergistic with simvastatin. Cycloheximide chase assay, in vivo ubiquitination assay, LDL-C uptake assay, qRT-PCR Scientific reports Medium 33199761
2017 miR-19b directly downregulates MYLIP through its 3'-UTR, promoting breast cancer cell migration and metastasis. Overexpression of miR-19b or inhibition of MYLIP facilitates migration/invasion; MYLIP suppression by miR-19b alters cell adhesion molecule expression (E-Cadherin down, ICAM-1 and Integrin β1 up) and activates Ras-MAPK and PI3K-AKT pathways in vitro and in vivo. 3'-UTR luciferase reporter assay, wound healing and transwell invasion assay, mouse tumor growth model, Western blot Oncotarget Medium 28969074
2020 LncRNA TUSC8 functions as a competing endogenous RNA (ceRNA) sponging miR-190b-5p, thereby preventing miR-190b-5p from suppressing MYLIP expression. TUSC8 knockdown promotes breast cancer proliferation, migration, and invasion in vitro and in vivo, at least partly through reducing MYLIP levels and modulating EMT markers. Luciferase reporter assay, RIP assay, RNA pull-down, siRNA knockdown, mouse xenograft model Aging Medium 32039833

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 miR-15 and miR-16 induce apoptosis by targeting BCL2. Proceedings of the National Academy of Sciences of the United States of America 2838 16166262
2009 LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. Science (New York, N.Y.) 675 19520913
2009 Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype. Nature medicine 536 19898489
2009 miR-19 is a key oncogenic component of mir-17-92. Genes & development 523 20008935
2013 Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis. The Journal of clinical investigation 278 23921124
2010 miR-126 and miR-126*: new players in cancer. TheScientificWorldJournal 184 20953557
2014 MitomiRs in human inflamm-aging: a hypothesis involving miR-181a, miR-34a and miR-146a. Experimental gerontology 169 24607549
2009 CHANGES IN microRNA (miR) profile and effects of miR-320 in insulin-resistant 3T3-L1 adipocytes. Clinical and experimental pharmacology & physiology 168 19473196
2016 Improving cell mixture deconvolution by identifying optimal DNA methylation libraries (IDOL). BMC bioinformatics 148 26956433
2014 miR-1, miR-10b, miR-155, and miR-191 are novel regulators of BDNF. Cellular and molecular life sciences : CMLS 136 24804980
2009 Gfi1 regulates miR-21 and miR-196b to control myelopoiesis. Blood 124 19278956
2010 miR-29b and miR-125a regulate podoplanin and suppress invasion in glioblastoma. Genes, chromosomes & cancer 122 20665731
2011 PPARα is regulated by miR-21 and miR-27b in human liver. Pharmaceutical research 116 21562928
2010 The E3 ubiquitin ligase IDOL induces the degradation of the low density lipoprotein receptor family members VLDLR and ApoER2. The Journal of biological chemistry 116 20427281
2019 miR-15a-5p, miR-15b-5p, and miR-16-5p inhibit tumor progression by directly targeting MYCN in neuroblastoma. Molecular oncology 110 31637848
2015 miR-24, miR-30b, and miR-142-3p regulate phagocytosis in myeloid inflammatory cells. Journal of immunology (Baltimore, Md. : 1950) 110 25601927
2014 MiR-143 and MiR-145 regulate IGF1R to suppress cell proliferation in colorectal cancer. PloS one 108 25474488
2014 MDRL lncRNA regulates the processing of miR-484 primary transcript by targeting miR-361. PLoS genetics 104 25057983
2012 Feedback regulation of cholesterol uptake by the LXR-IDOL-LDLR axis. Arteriosclerosis, thrombosis, and vascular biology 100 22936343
2013 Dysregulation of miR-106a and miR-591 confers paclitaxel resistance to ovarian cancer. British journal of cancer 98 23807165
2011 miR-21 and miR-214 are consistently modulated during renal injury in rodent models. The American journal of pathology 93 21704009
2018 The function of miR-143, miR-145 and the MiR-143 host gene in cardiovascular development and disease. Vascular pharmacology 90 30502421
2017 LncRNA GAS5 suppresses the tumorigenesis of cervical cancer by downregulating miR-196a and miR-205. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 85 28671039
2017 miR-34a and miR-34b/c Suppress Intestinal Tumorigenesis. Cancer research 79 28363996
2014 The LXR-Idol axis differentially regulates plasma LDL levels in primates and mice. Cell metabolism 79 25440061
2019 Assessment of miR-98-5p, miR-152-3p, miR-326 and miR-4289 Expression as Biomarker for Prostate Cancer Diagnosis. International journal of molecular sciences 78 30845775
2015 miR-93/miR-106b/miR-375-CIC-CRABP1: a novel regulatory axis in prostate cancer progression. Oncotarget 78 26124181
2019 MiR-139-5p, miR-940 and miR-193a-5p inhibit the growth of hepatocellular carcinoma by targeting SPOCK1. Journal of cellular and molecular medicine 77 30710422
2013 miR-214 coordinates melanoma progression by upregulating ALCAM through TFAP2 and miR-148b downmodulation. Cancer research 77 23667173
2015 miR-346 and miR-138 competitively regulate hTERT in GRSF1- and AGO2-dependent manners, respectively. Scientific reports 74 26507454
2014 Mir-23b and miR-130b expression is downregulated in pituitary adenomas. Molecular and cellular endocrinology 73 24681352
2011 The IDOL-UBE2D complex mediates sterol-dependent degradation of the LDL receptor. Genes & development 73 21685362
2013 IDOL stimulates clathrin-independent endocytosis and multivesicular body-mediated lysosomal degradation of the low-density lipoprotein receptor. Molecular and cellular biology 72 23382078
2017 Early diagnostic evaluation of miR-122 and miR-224 as biomarkers for hepatocellular carcinoma. Genes & diseases 71 30258925
2014 miR-1 and miR-145 act as tumor suppressor microRNAs in gallbladder cancer. International journal of clinical and experimental pathology 71 24966896
2019 MiR‑30e and miR‑92a are related to atherosclerosis by targeting ABCA1. Molecular medicine reports 70 30816508
2015 The Effect of miR-132, miR-146a, and miR-155 on MRP8/TLR4-Induced Astrocyte-Related Inflammation. Journal of molecular neuroscience : MN 65 25957996
2013 miR-19a and miR-19b overexpression in gliomas. Pathology oncology research : POR 65 23824915
2011 MicroRNAs miR-27a and miR-143 regulate porcine adipocyte lipid metabolism. International journal of molecular sciences 65 22174642
2016 Tumor-suppressing roles of miR-214 and miR-218 in breast cancer. Oncology reports 63 27109339
2012 Fibroblast growth factor-21 (FGF21) regulates low-density lipoprotein receptor (LDLR) levels in cells via the E3-ubiquitin ligase Mylip/Idol and the Canopy2 (Cnpy2)/Mylip-interacting saposin-like protein (Msap). The Journal of biological chemistry 61 22378787
2013 The LXR-IDOL axis defines a clathrin-, caveolae-, and dynamin-independent endocytic route for LDLR internalization and lysosomal degradation. Journal of lipid research 60 23733886
2016 Regulation of miR-200c and miR-141 by Methylation in Prostate Cancer. The Prostate 56 27198154
2019 The microRNAs miR-449a and miR-424 suppress osteosarcoma by targeting cyclin A2 expression. The Journal of biological chemistry 55 30679313
2011 The N342S MYLIP polymorphism is associated with high total cholesterol and increased LDL receptor degradation in humans. The Journal of clinical investigation 54 21765216
2018 Bergapten inhibits liver carcinogenesis by modulating LXR/PI3K/Akt and IDOL/LDLR pathways. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 53 30227322
2017 miR-125a, miR-139 and miR-324 contribute to Urocortin protection against myocardial ischemia-reperfusion injury. Scientific reports 53 28827743
2015 miR-27a and miR-27a* contribute to metastatic properties of osteosarcoma cells. Oncotarget 53 25749032
2013 miR-25 and miR-92a regulate insulin I biosynthesis in rats. RNA biology 47 24084692
2011 Distinct functional domains contribute to degradation of the low density lipoprotein receptor (LDLR) by the E3 ubiquitin ligase inducible Degrader of the LDLR (IDOL). The Journal of biological chemistry 47 21734303
2015 miR-23a binds to p53 and enhances its association with miR-128 promoter. Scientific reports 44 26553132
2015 The Deubiquitylase USP2 Regulates the LDLR Pathway by Counteracting the E3-Ubiquitin Ligase IDOL. Circulation research 44 26666640
2018 A urinary microRNA (miR) signature for diagnosis of bladder cancer. Urologic oncology 43 30322728
2013 MiR-216a and miR-216b as markers for acute phased pancreatic injury. Biomedical research (Tokyo, Japan) 43 23995054
2013 Acarbose reduces blood glucose by activating miR-10a-5p and miR-664 in diabetic rats. PloS one 43 24260283
2018 miR-103/miR-195/miR-15b Regulate SALL4 and Inhibit Proliferation and Migration in Glioma. Molecules (Basel, Switzerland) 42 30423818
2017 miR-19b promotes breast cancer metastasis through targeting MYLIP and its related cell adhesion molecules. Oncotarget 41 28969074
2019 MiR-34 and MiR-200: Regulator of Cell Fate Plasticity and Neural Development. Neuromolecular medicine 38 30963386
2017 miR-149 and miR-29c as candidates for bipolar disorder biomarkers. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 38 28190298
2015 Deregulation of miR-93 and miR-143 in human esophageal cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 38 26427659
2015 A MARCH6 and IDOL E3 Ubiquitin Ligase Circuit Uncouples Cholesterol Synthesis from Lipoprotein Uptake in Hepatocytes. Molecular and cellular biology 38 26527619
2018 miR-223/Hsp70/JNK/JUN/miR-223 feedback loop modulates the chemoresistance of osteosarcoma to cisplatin. Biochemical and biophysical research communications 37 29432736
2017 Regulation of PLK1 through competition between hnRNPK, miR-149-3p and miR-193b-5p. Cell death and differentiation 37 28708135
2014 MiR-520d-5p directly targets TWIST1 and downregulates the metastamiR miR-10b. Oncotarget 36 25426550
2010 Suppression of Idol expression is an additional mechanism underlying statin-induced up-regulation of hepatic LDL receptor expression. International journal of molecular medicine 34 21069265
2020 Long non-coding RNA TUSC8 inhibits breast cancer growth and metastasis via miR-190b-5p/MYLIP axis. Aging 33 32039833
2021 LncRNA APCDD1L-AS1 induces icotinib resistance by inhibition of EGFR autophagic degradation via the miR-1322/miR-1972/miR-324-3p-SIRT5 axis in lung adenocarcinoma. Biomarker research 32 33516270
2017 Serum miR-146a, miR-155, and miR-210 as potential markers of Graves' disease. Journal of clinical laboratory analysis 31 28569050
2017 The lncRNA XIST interacts with miR-140/miR-124/iASPP axis to promote pancreatic carcinoma growth. Oncotarget 31 29371940
2014 MiR-421, miR-155 and miR-650: emerging trends of regulation of cancer and apoptosis. Asian Pacific journal of cancer prevention : APJCP 30 24716910
2020 Thymoquinone potentiates miR-16 and miR-375 expressions in hepatocellular carcinoma. Life sciences 29 32422307
2020 Platycodin D enhances LDLR expression and LDL uptake via down-regulation of IDOL mRNA in hepatic cells. Scientific reports 29 33199761
2019 Shear stress regulation of miR-93 and miR-484 maturation through nucleolin. Proceedings of the National Academy of Sciences of the United States of America 29 31182601
2018 MiR-192, miR-200c and miR-17 are fibroblast-mediated inhibitors of colorectal cancer invasion. Oncotarget 29 30473751
2012 Liver X receptors agonists impede hepatitis C virus infection in an Idol-dependent manner. Antiviral research 28 22713431
2021 MiR-574-5P, miR-1827, and miR-4429 as Potential Biomarkers for Schizophrenia. Journal of molecular neuroscience : MN 27 34811713
2018 Bioselection Reveals miR-99b and miR-485 as Enhancers of Adenoviral Oncolysis in Pancreatic Cancer. Molecular therapy : the journal of the American Society of Gene Therapy 27 30341009
2015 Overexpression of miR-21 and miR-122 in preeclamptic placentas. Neuro endocrinology letters 27 26859593
2013 Proteome modulation in H9c2 cardiac cells by microRNAs miR-378 and miR-378. Molecular & cellular proteomics : MCP 26 24068033
2020 MIR-107, MIR-223-3P and MIR-21-5P Reveals Potential Biomarkers in Penile Cancer. Asian Pacific journal of cancer prevention : APJCP 25 32102516
2018 Inactivation of the E3 Ubiquitin Ligase IDOL Attenuates Diet-Induced Obesity and Metabolic Dysfunction in Mice. Arteriosclerosis, thrombosis, and vascular biology 25 29903737
2018 Expression of circulating miR-17, miR-25, and miR-133 in breast cancer patients. Journal of cellular biochemistry 25 30485486
2017 The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning. eLife 25 28891791
2015 IDOL, inducible degrader of low-density lipoprotein receptor, serves as a potential therapeutic target for dyslipidemia. Medical hypotheses 25 26601593
2014 Transgenic expression of dominant-active IDOL in liver causes diet-induced hypercholesterolemia and atherosclerosis in mice. Circulation research 25 24935961
2020 LDL Receptor Pathway Regulation by miR-224 and miR-520d. Frontiers in cardiovascular medicine 24 32528976
2016 miR-203 and miR-221 regulate SOCS1 and SOCS3 in essential thrombocythemia. Blood cancer journal 24 26990535
2020 miR-9, miR-21, miR-27b, and miR-34a Expression in HPV16/58/52-Infected Cervical Cancer. BioMed research international 22 33015156
2015 miR-31 and miR-17-5p levels change during transformation of follicular lymphoma. Human pathology 22 26997445
2022 APE1 controls DICER1 expression in NSCLC through miR-33a and miR-130b. Cellular and molecular life sciences : CMLS 21 35876890
2015 Deubiquitylase Inhibition Reveals Liver X Receptor-independent Transcriptional Regulation of the E3 Ubiquitin Ligase IDOL and Lipoprotein Uptake. The Journal of biological chemistry 21 26719329
2014 Expressions of miR-22 and miR-135a in acute pancreatitis. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 21 24710937
2013 miR deregulation in CLL. Advances in experimental medicine and biology 21 24014303
2021 Upregulation of miR-3195, miR-3687 and miR-4417 is associated with castration-resistant prostate cancer. World journal of urology 20 33990872
2019 IDOL regulates systemic energy balance through control of neuronal VLDLR expression. Nature metabolism 20 32072135
2022 miR-1269a and miR-1269b: Emerging Carcinogenic Genes of the miR-1269 Family. Frontiers in cell and developmental biology 19 35252180
2020 SUMOylation of the ubiquitin ligase IDOL decreases LDL receptor levels and is reversed by SENP1. The Journal of biological chemistry 19 33154164
2016 Post-transcriptional Regulation of BRCA2 through Interactions with miR-19a and miR-19b. Frontiers in genetics 19 27630665
2013 Reciprocal regulation of very low density lipoprotein receptors (VLDLRs) in neurons by brain-derived neurotrophic factor (BDNF) and Reelin: involvement of the E3 ligase Mylip/Idol. The Journal of biological chemistry 19 23990472
2018 Biological role of miR-204 and miR-211 in melanoma. Oncoscience 18 30234146