Affinage

PDLIM4

PDZ and LIM domain protein 4 · UniProt P50479

Length
330 aa
Mass
35.4 kDa
Annotated
2026-04-29
100 papers in source corpus 12 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDLIM4 (RIL) is a PDZ-LIM domain adaptor protein that scaffolds cytoskeletal and signaling complexes on actin stress fibers, thereby controlling actin dynamics, cell motility, and receptor trafficking in diverse cell types. Its PDZ domain binds α-actinin (and the phosphatase PTP-BL), while its LIM domain engages the AMPA receptor subunit GluR-A; in neurons, PDLIM4 directs GluR-A-containing AMPA receptors to dendritic spines in an α-actinin/actin-dependent manner, increasing synaptic strength (PMID:15456832, PMID:14729062). In immune cells, PDLIM4 interacts with S1P1 and F-actin to regulate CD4+ T-cell egress from the thymus and dendritic cell migration via the CCR7–JNK pathway (PMID:31393857, PMID:31287961). An alternatively spliced isoform lacking a functional LIM domain (RILaltCterm) acts as a dominant-negative modulator subject to ubiquitin-independent 20S proteasomal degradation that is stabilized by NQO1 under oxidative stress, providing a stress-responsive mechanism for tuning actin remodeling; PDLIM4 expression is epigenetically silenced by promoter hypermethylation in several cancers, and its re-expression suppresses proliferation and enhances apoptosis in colon and prostate cancer cells (PMID:21636573, PMID:17332327, PMID:19212833).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1998 Medium

    Establishing the genomic architecture of PDLIM4 revealed that the LIM domain is encoded by the two 3′ exons and that alternative splicing can eliminate the LIM domain, raising the question of whether the two isoforms have distinct functions.

    Evidence Southern blot and restriction mapping of YAC/cosmid clones, RT-PCR of human fetal brain mRNA

    PMID:9573374

    Open questions at the time
    • Functional significance of LIM-less isoform not yet tested
    • Promoter regulation not characterized
  2. 2004 High

    Concurrent studies established that PDLIM4 is a bona fide actin stress-fiber-associated scaffold: its PDZ domain recruits α-actinin and enhances α-actinin–actin co-sedimentation, while its LIM domain binds the GluR-A AMPA receptor, enabling receptor delivery to dendritic spines and increased synaptic transmission—answering how PDZ-LIM proteins couple receptor trafficking to the actin cytoskeleton.

    Evidence Co-IP, in vitro co-sedimentation, live-cell EGFP imaging, subcellular fractionation, mEPSC recording in cultured neurons

    PMID:14729062 PMID:15456832

    Open questions at the time
    • In vivo confirmation of PDLIM4-dependent AMPA receptor trafficking not performed
    • Whether the LIM domain binds actin directly or only via GluR-A was unresolved
  3. 2004 Medium

    Identification of PTP-BL as a PDZ-mediated interactor of PDLIM4, with NMR titration showing the LIM domain synergistically enhances binding, broadened the adaptor's interaction network beyond α-actinin to include phosphatase signaling.

    Evidence NMR titration, site-directed mutagenesis, Co-IP in mammalian cell lysates

    PMID:15663004

    Open questions at the time
    • Functional consequence of PDLIM4–PTP-BL interaction on phosphatase activity or substrate access not tested
    • No in vivo validation
  4. 2007 Medium

    Demonstration that PDLIM4 is silenced by promoter hypermethylation in cancer and that its re-expression suppresses growth and promotes UV-induced apoptosis established a tumor-suppressor function, explaining how loss of this cytoskeletal adaptor contributes to oncogenesis.

    Evidence Methylation-specific PCR, stable transfection re-expression in colon cancer cells, apoptosis and clonogenicity assays

    PMID:17332327

    Open questions at the time
    • Mechanism linking actin scaffolding to growth suppression and apoptosis sensitization not defined
    • In vivo tumor suppression not shown in this study
  5. 2009 Medium

    Direct binding of PDLIM4 to F-actin was confirmed and re-expression in prostate cancer cells caused G1 arrest and reduced xenograft growth, extending the tumor-suppressor role to a second cancer type and establishing a direct F-actin interaction.

    Evidence F-actin binding assay, cell cycle analysis, xenograft tumor model in prostate cancer cells

    PMID:19212833

    Open questions at the time
    • Molecular mechanism of G1 arrest not identified
    • Single cancer model
  6. 2011 High

    Discovery that the LIM-less splice isoform (RILaltCterm) is a dominant-negative modulator degraded by the 20S proteasome in a ubiquitin-independent manner—and stabilized by NQO1 under oxidative stress—revealed a built-in regulatory circuit for tuning PDLIM4 activity on actin.

    Evidence Overexpression/dominant-negative analysis, proteasome degradation assays, NQO1 co-expression/binding, actin imaging, motility assays

    PMID:21636573

    Open questions at the time
    • Physiological contexts in which NQO1-mediated stabilization operates in vivo not demonstrated
    • Stoichiometry of full-length vs. alternative isoform under native conditions unknown
  7. 2012 Medium

    Knockdown studies showed that PDLIM4 and the related adaptor CLP36 have overlapping but functionally distinct roles in recruiting α-actinin-1 and palladin to stress fibers, with PDLIM4 specifically stabilizing fibers—clarifying how multiple ALP-family proteins collaborate on the same structures.

    Evidence siRNA knockdown, Co-IP, time-lapse live imaging, immunofluorescence

    PMID:22659164

    Open questions at the time
    • Whether PDLIM4 and CLP36 compensate for each other in vivo untested
    • Palladin interaction with PDLIM4 not characterized at the domain level
  8. 2019 High

    Two studies established PDLIM4 as a critical immune-cell migration adaptor: it scaffolds S1P1 and F-actin to control CD4+ T-cell thymic egress (regulated transcriptionally by JMJD3/KLF2), and it promotes dendritic cell migration and maturation via the CCR7–JNK pathway, answering how a cytoskeletal adaptor influences adaptive immunity.

    Evidence ChIP-seq, Co-IP of PDLIM4–S1P1–F-actin, in vivo T-cell trafficking assay, shRNA knockdown in DCs, in vivo DC migration, Transwell migration

    PMID:31287961 PMID:31393857

    Open questions at the time
    • Whether PDLIM4 directly bridges S1P1 to actin or requires intermediary adaptors not resolved
    • Structural basis for PDLIM4–S1P1 interaction unknown
    • DC-specific vs. general migratory function not delineated
  9. 2020 Medium

    In breast cancer, elevated PDLIM4 promotes migration and xenograft metastasis without correlating with Src inhibition, revealing a context-dependent pro-migratory role that contrasts with its tumor-suppressor function in colon and prostate cancer—demonstrating tissue-specific duality.

    Evidence RNAi knockdown, ectopic overexpression, migration assay, xenograft tumor formation, Src activity measurement

    PMID:32002121

    Open questions at the time
    • Signaling pathway through which PDLIM4 promotes breast cancer cell motility not identified
    • No mechanism distinguishing tumor-suppressive vs. pro-migratory contexts
  10. 2022 Medium

    Identification of a circ0002360/miR-629-3p/PDLIM4 axis in gastric cancer showed that post-transcriptional regulation of PDLIM4 levels can promote proliferation and suppress oxidative stress, adding a non-coding RNA regulatory layer to PDLIM4 biology.

    Evidence RNA immunoprecipitation, dual-luciferase reporter assay, functional overexpression/knockdown assays, DCFH-DA oxidative stress assay

    PMID:35982735

    Open questions at the time
    • Mechanism by which PDLIM4 suppresses oxidative stress not characterized
    • Single cell-line system
    • Apparent pro-proliferative role conflicts with tumor-suppressor data in other tissues—unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for PDLIM4's domain-specific interactions, how tissue context switches its role between tumor suppression and migration promotion, and the physiological regulation of the full-length vs. dominant-negative isoform balance in vivo.
  • No crystal or cryo-EM structure of PDLIM4 or its complexes
  • No genetic model (knockout mouse phenotype) fully characterized
  • Mechanism determining tumor-suppressive vs. pro-migratory outcome across tissues unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 5 GO:0060090 molecular adaptor activity 3
Localization
GO:0005856 cytoskeleton 4
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2 R-HSA-112316 Neuronal System 1
Complex memberships
α-actinin-1/palladin/PDLIM4 stress fiber complex

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 RIL (PDLIM4) binds to the AMPA receptor subunit GluR-A C-terminal peptide via its LIM domain and to α-actinin via its PDZ domain; RIL is enriched in the postsynaptic density fraction and co-precipitates with α-actinin in AMPA receptor immunoprecipitates from forebrain synaptosomes; overexpression of RIL increases AMPA receptor accumulation in dendritic spines and synaptic miniature EPSC amplitude, indicating RIL directs GluR-A-containing AMPA receptor transport to dendritic spines in an α-actinin/actin-dependent manner. Co-immunoprecipitation, subcellular fractionation, in vitro binding assays, overexpression in cultured neurons with immunodetection and mEPSC recording The Journal of neuroscience High 15456832
2004 RIL (PDLIM4) localizes to actin stress fibers in nonmuscle epithelial cells, associates with α-actinin via its PDZ domain, and enhances the ability of α-actinin to co-sediment with actin filaments; RIL expression leads to abnormal thick irregular stress fibers and altered stress fiber dynamics including rapid formation and frequent collapse of fibers, as observed by live-cell imaging. Immunofluorescence localization, in vitro co-sedimentation assay, live-cell EGFP imaging, co-immunoprecipitation Experimental cell research High 14729062
2009 PDLIM4 directly interacts with F-actin in prostate cancer cells; re-expression of PDLIM4 reduces cell growth, clonogenicity, and causes G1 cell-cycle arrest, and reduces tumor growth in xenografts, supporting a role in controlling cell proliferation through actin association. F-actin binding assay (direct interaction with F-actin), cell growth and clonogenicity assays, cell cycle analysis, xenograft tumor model Cancer investigation Medium 19212833
2007 RIL (PDLIM4), a LIM domain gene at 5q31, is silenced by promoter hypermethylation in cancer; restoration of RIL expression in colon cancer cells by stable transfection reduces cell growth and clonogenicity and increases apoptosis following UV exposure, indicating RIL functions as a tumor suppressor. Stable transfection re-expression, methylation-specific PCR, cell growth/clonogenicity assays, apoptosis assay Cancer research Medium 17332327
2011 The alternatively spliced isoform of RIL (RILaltCterm, product of PDLIM4) acts as a dominant-negative modulator of RIL-mediated actin reorganization; RILaltCterm has a disordered alternative C-terminal segment directing it to ubiquitin-independent degradation by the core 20S proteasome, which is blocked by binding to NQO1 (NAD(P)H quinone oxidoreductase) induced by oxidative stress; overexpression or stabilization of RILaltCterm counteracts full-length RIL effects on actin cytoskeleton organization and cell motility. Overexpression/dominant-negative analysis, proteasome degradation assays, NQO1 co-expression/binding, actin organization imaging, cell motility assays The Journal of biological chemistry High 21636573
2012 CLP36 and RIL (PDLIM4) both form a complex with α-actinin-1 and palladin on stress fibers; loss of CLP36/RIL correlates with failure of α-actinin-1 and palladin to localize on stress fibers; RIL stabilizes stress fibers while CLP36 influences their dynamic architecture, demonstrating a redundant but functionally distinct role for the two proteins in stress fiber formation. siRNA knockdown, co-immunoprecipitation, time-lapse live imaging, immunofluorescence localization Experimental cell research Medium 22659164
2019 JMJD3 (histone H3K27 demethylase) binds to the promoter and gene body of Pdlim4 and regulates its expression by interacting with the zinc finger transcription factor KLF2; JMJD3 deficiency in CD4+ T cells reduces PDLIM4 expression, and PDLIM4 functions as an adaptor protein interacting with S1P1 and filamentous actin (F-actin) to regulate T cell trafficking—JMJD3-deficient or PDLIM4-deficient CD4+ T cells accumulate in the thymus and are reduced in secondary lymphoid organs. ChIP-seq, gene expression profiling, Co-immunoprecipitation (PDLIM4–S1P1–F-actin interaction), T cell trafficking in vivo assay, knockdown/knockout The Journal of clinical investigation High 31393857
2019 PDLIM4 is required for mature dendritic cell (DC) migration via the CCR7-JNK signaling pathway and for F-actin-dependent dendrite formation; Pdlim4 knockdown in DCs reduces expression of antigen-presentation and co-stimulatory molecules, cytokine production, T-cell activation capacity, and in vivo migration to draining lymph nodes. Lentiviral shRNA knockdown, Transwell migration assay, in vivo DC migration (footpad injection/flow cytometry), confocal microscopy (dendrite morphology), Western blotting, flow cytometry, ELISA FASEB journal High 31287961
2004 RIL (PDLIM4) interacts with the PDZ domains of PTP-BL protein tyrosine phosphatase via its C-terminus, with the LIM domain playing a synergistic (but not primary binding-surface) role in enhancing this interaction, as demonstrated by NMR titration and site-directed mutagenesis. Co-immunoprecipitation in mammalian cell lysates, NMR titration, site-directed mutagenesis Molecular biology reports Medium 15663004
2020 In breast cancer cell lines, elevated RIL (PDLIM4) levels are associated with increased cell migratory activity and increased incidence of xenograft formation and metastasis; no direct correlation between RIL expression and Src kinase activity was detected, arguing against a simple Src-inhibitory mechanism and suggesting context-dependent oncogenic roles for RIL in promoting cell motility. RNAi knockdown, ectopic overexpression, cell migration assay, xenograft tumor formation, Src activity measurement Oncotarget Medium 32002121
2022 circ0002360 sponges miR-629-3p, which targets PDLIM4 mRNA; reduced miR-629-3p allows increased PDLIM4 expression; PDLIM4 upregulation downstream of this axis promotes gastric cancer cell proliferation and migration while inhibiting oxidative stress. RNA immunoprecipitation (RIP), dual-luciferase reporter assay, overexpression/knockdown functional assays (clone formation, Transwell), DCFH-DA oxidative stress assay Oxidative medicine and cellular longevity Medium 35982735
1998 The human RIL gene (PDLIM4) maps to chromosome 5q31.1, approximately 240–260 kb telomeric to IRF1; the gene spans 14.5 kb with seven exons, with the two 3'-exons encoding the LIM domain; an alternative transcript lacking exon 6 results in loss of the LIM domain; two putative transcription start points were identified in the 5'-flanking region. Southern blot, restriction mapping of YAC and cosmid clones, PCR of human fetal brain mRNA, genomic sequencing Gene Medium 9573374

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1985 Leu-11+ lymphocytes with natural killer (NK) activity are precursors of recombinant interleukin 2 (rIL 2)-induced activated killer (AK) cells. Journal of immunology (Baltimore, Md. : 1950) 301 3917475
1985 Generation of activated killer (AK) cells by recombinant interleukin 2 (rIL 2) in collaboration with interferon-gamma (IFN-gamma). Journal of immunology (Baltimore, Md. : 1950) 206 2984283
1995 Systemic administration of rIL-12 induces complete tumor regression and protective immunity: response is correlated with a striking reversal of suppressed IFN-gamma production by anti-tumor T cells. International immunology 196 8527411
2007 Identification of metabolic and biomass QTL in Arabidopsis thaliana in a parallel analysis of RIL and IL populations. The Plant journal : for cell and molecular biology 147 18047556
1987 Phenotypic and functional characterization of recombinant interleukin 2 (rIL 2)-induced activated killer cells: analysis at the population and clonal levels. Journal of immunology (Baltimore, Md. : 1950) 133 3100633
2009 Quantitative trait loci conferring grain mineral nutrient concentrations in durum wheat x wild emmer wheat RIL population. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 128 19407982
1998 Immune suppression by recombinant interleukin (rIL)-12 involves interferon gamma induction of nitric oxide synthase 2 (iNOS) activity: inhibitors of NO generation reveal the extent of rIL-12 vaccine adjuvant effect. The Journal of experimental medicine 105 9802972
1988 Intralesional infusion of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) for the treatment of patients with malignant brain tumor. Neurosurgery 97 2851116
2006 PDLIM4 repression by hypermethylation as a potential biomarker for prostate cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 96 16489065
1990 Induction of germ-line and mature C epsilon transcripts in human B cells stimulated with rIL-4 and EBV. Journal of immunology (Baltimore, Md. : 1950) 92 2172384
2006 Molecular genetic analysis of five spike-related traits in wheat using RIL and immortalized F2 populations. Molecular genetics and genomics : MGG 88 17033810
2004 Actin/alpha-actinin-dependent transport of AMPA receptors in dendritic spines: role of the PDZ-LIM protein RIL. The Journal of neuroscience : the official journal of the Society for Neuroscience 87 15456832
1996 Molecular mechanisms underlying IFN-gamma-mediated tumor growth inhibition induced during tumor immunotherapy with rIL-12. International immunology 86 8671675
2008 Lysis of endogenously infected CD4+ T cell blasts by rIL-2 activated autologous natural killer cells from HIV-infected viremic individuals. PLoS pathogens 82 18617991
2014 Mapping QTLs of yield-related traits using RIL population derived from common wheat and Tibetan semi-wild wheat. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 80 25208643
2004 The PDZ-LIM protein RIL modulates actin stress fiber turnover and enhances the association of alpha-actinin with F-actin. Experimental cell research 77 14729062
2017 Mapping the small RNA interactome in bacteria using RIL-seq. Nature protocols 75 29215635
2010 Meta-analysis of cotton fiber quality QTLs across diverse environments in a Gossypium hirsutum x G. barbadense RIL population. BMC plant biology 72 20584292
2011 Molecular insights on the peripheral and intratumoral effects of systemic high-dose rIL-2 (aldesleukin) administration for the treatment of metastatic melanoma. Clinical cancer research : an official journal of the American Association for Cancer Research 69 21976537
2011 An integrated genetic linkage map of cultivated peanut (Arachis hypogaea L.) constructed from two RIL populations. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 60 22072100
2007 RIL, a LIM gene on 5q31, is silenced by methylation in cancer and sensitizes cancer cells to apoptosis. Cancer research 56 17332327
1992 Decrease in HIV provirus in peripheral blood mononuclear cells during zidovudine and human rIL-2 administration. Journal of acquired immune deficiency syndromes 53 1738087
2009 A new interspecific, Gossypium hirsutum x G. barbadense, RIL population: towards a unified consensus linkage map of tetraploid cotton. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 51 19387609
1995 Cloning of a rat cDNA encoding a novel LIM domain protein with high homology to rat RIL. Gene 50 8522188
2010 Mapping of QTLs for morpho-agronomic and seed quality traits in a RIL population of common bean (Phaseolus vulgaris L.). TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 46 20084493
2012 Methylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancer is associated with clinical characteristics, but only RASSF1A methylation is associated with outcome. BMC cancer 45 22695491
1987 Assignment of the Ly-6--Ril-1--Sis--H-30--Pol-5/Xmmv-72--Ins-3--Krt-1--Int-1 --Gdc-1 region to mouse chromosome 15. Immunogenetics 44 2885263
2020 High-Resolution Mapping in Two RIL Populations Refines Major "QTL Hotspot" Regions for Seed Size and Shape in Soybean (Glycine max L.). International journal of molecular sciences 43 32033213
2016 SNP discovery and genetic mapping using genotyping by sequencing of whole genome genomic DNA from a pea RIL population. BMC genomics 42 26892170
1988 Recombinant interleukin-2 (rIL-2) improves immune response and host resistance to septic challenge in thermally injured mice. Surgery 41 3261049
2015 Wide-genome QTL mapping of fruit quality traits in a tomato RIL population derived from the wild-relative species Solanum pimpinellifolium L. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 35 26163766
1996 Subcutaneous recombinant interleukin-2 (rIL-2) in out-patients with metastatic renal cell carcinoma. Results of a multicenter SCAPP1 trial. Annals of oncology : official journal of the European Society for Medical Oncology 35 8839910
2016 QTL Mapping of Low-Temperature Germination Ability in the Maize IBM Syn4 RIL Population. PloS one 34 27031623
2009 PDLIM4, an actin binding protein, suppresses prostate cancer cell growth. Cancer investigation 34 19212833
2012 Genetic control of soybean seed oil: I. QTL and genes associated with seed oil concentration in RIL populations derived from crossing moderately high-oil parents. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 33 23192670
2011 A phase I study of recombinant human interleukin-21 (rIL-21) in combination with sunitinib in patients with metastatic renal cell carcinoma (RCC). Acta oncologica (Stockholm, Sweden) 33 21174612
2020 Identification of the vernalization gene VRN-B1 responsible for heading date variation by QTL mapping using a RIL population in wheat. BMC plant biology 31 32660420
1993 Enhancement of anti-tumor activity of recombinant interleukin-2 (rIL-2) by immunocomplexing with a monoclonal antibody against rIL-2. Biotherapy (Dordrecht, Netherlands) 31 8292462
2014 Mapping genomic loci for cotton plant architecture, yield components, and fiber properties in an interspecific (Gossypium hirsutum L. × G. barbadense L.) RIL population. Molecular genetics and genomics : MGG 30 25314923
2017 Updated foxtail millet genome assembly and gene mapping of nine key agronomic traits by resequencing a RIL population. GigaScience 29 28369461
2011 Identification of QTLs for seed germination capability after various storage periods using two RIL populations in rice. Molecules and cells 28 21399992
1987 rIL 2-induced proliferation of human circulating NK cells and T lymphocytes: synergistic effects of IL 1 and IL 2. Journal of immunology (Baltimore, Md. : 1950) 28 3110271
2015 New QTL alleles for quality-related traits in spring wheat revealed by RIL population derived from supernumerary × non-supernumerary spikelet genotypes. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 27 25740563
1990 Cytotoxic events taking place in the lung of patients with HIV-1 infection. Evidence of an intrinsic defect of the major histocompatibility complex-unrestricted killing partially restored by the incubation with rIL-2. The American review of respiratory disease 27 2389902
2019 Utilization of Interspecific High-Density Genetic Map of RIL Population for the QTL Detection and Candidate Gene Mining for 100-Seed Weight in Soybean. Frontiers in plant science 25 31552060
2020 Mapping QTL for agronomic traits under two levels of salt stress in a new constructed RIL wheat population. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 24 32995899
1998 The human RIL gene: mapping to human chromosome 5q31.1, genomic organization and alternative transcripts. Gene 24 9573374
2021 Prediction of Novel Bacterial Small RNAs From RIL-Seq RNA-RNA Interaction Data. Frontiers in microbiology 23 34093460
2018 Efficient QTL detection of flowering date in a soybean RIL population using the novel restricted two-stage multi-locus GWAS procedure. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 23 30167759
1991 High-level production of murine interleukin-5 (IL-5) utilizing recombinant baculovirus expression. Purification of the rIL-5 and its use in assessing the biologic role of IL-5 glycosylation. Cytokine 23 1883961
2021 Physiological and genetic characterization of heat stress effects in a common bean RIL population. PloS one 22 33914759
2021 QTL mapping of seedling tolerance to exposure to low temperature in the maize IBM RIL population. PloS one 22 34242344
2013 QTL mapping of slow-rusting, adult plant resistance to race Ug99 of stem rust fungus in PBW343/Muu RIL population. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 21 23440380
1993 Immunological and clinical effects of intramuscular rIFN alpha-2a and low dose subcutaneous rIL-2 in patients with advanced malignant melanoma. Melanoma research 21 8471836
2020 QTL mapping of yield component traits on bin map generated from resequencing a RIL population of foxtail millet (Setaria italica). BMC genomics 20 32041544
2020 Molecular mapping of QTLs for yield related traits in recombinant inbred line (RIL) population derived from the popular rice hybrid KRH-2 and their validation through SNP genotyping. Scientific reports 20 32792551
2011 Actin cytoskeleton remodeling by the alternatively spliced isoform of PDLIM4/RIL protein. The Journal of biological chemistry 20 21636573
2023 Identification of major QTLs for soybean seed size and seed weight traits using a RIL population in different environments. Frontiers in plant science 19 36714756
2019 Attenuation of Allergen-, IL-13-, and TGF-α-induced Lung Fibrosis after the Treatment of rIL-15 in Mice. American journal of respiratory cell and molecular biology 19 30702923
2018 Genetic analysis and QTL mapping of the seed hardness trait in a black common bean (Phaseolus vulgaris) recombinant inbred line (RIL) population. Molecular breeding : new strategies in plant improvement 19 29568229
2016 QTLs for earliness and yield-forming traits in the Lubuski × CamB barley RIL population under various water regimes. Journal of applied genetics 19 27503092
2021 Dissecting the genetic control of seed coat color in a RIL population of common bean (Phaseolus vulgaris L.). TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 18 34328529
1987 Inverse relationship in H-2-associated lysis between NK cells and rIL-2-activated killer cells: evidence from in vitro killing and metastatic experiments. Cellular immunology 18 3496972
2019 JMJD3 regulates CD4 T cell trafficking by targeting actin cytoskeleton regulatory gene Pdlim4. The Journal of clinical investigation 17 31393857
2017 QTL mapping of selenium content using a RIL population in wheat. PloS one 16 28880898
2019 Pdlim4 is essential for CCR7-JNK-mediated dendritic cell migration and F-actin-related dendrite formation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 15 31287961
2014 QTL mapping of adult-plant resistance to leaf rust in a RIL population derived from a cross of wheat cultivars Shanghai 3/Catbird and Naxos. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 15 24970343
2010 Immunotherapy in high-risk chemotherapy-resistant patients with metastatic solid tumors and hematological malignancies using intentionally mismatched donor lymphocytes activated with rIL-2: a phase I study. Cancer immunology, immunotherapy : CII 15 20563804
1996 Immunologic and clinical modifications following low-dose subcutaneous administration of rIL-2 in non-Hodgkin's lymphoma patients after autologous bone marrow transplantation. Bone marrow transplantation 15 8831999
1995 The effects of rM-CSF and rIL-6 therapy on immunosuppressed antiorthostatically suspended mice. Journal of applied physiology (Bethesda, Md. : 1985) 15 7775343
1990 Recombinant interleukin-2 (rIL-2) with flavone acetic acid (FAA) in advanced malignant melanoma: a phase II study. British journal of cancer 15 2331447
2020 QTL mapping for soybean (Glycine max L.) leaf chlorophyll-content traits in a genotyped RIL population by using RAD-seq based high-density linkage map. BMC genomics 14 33096992
2019 Genetic Mapping and Validation of Quantitative Trait Loci (QTL) for the Grain Appearance and Quality Traits in Rice (Oryza sativa L.) by Using Recombinant Inbred Line (RIL) Population. International journal of genomics 14 30931320
1994 Treatment of advanced renal cell carcinoma using regional arterial administration of lymphokine-activated killer cells in combination with low doses of rIL-2. Urologia internationalis 14 7645136
2024 Genetic analysis and QTL mapping of seed hardness trait in a soybean (Glycine max) recombinant inbred line (RIL) population. Gene 13 38316262
2016 Expression of a Chimeric Allergen with High Rare Codons Content in Codon Bias-Adjusted Escherichia coli: Escherichia coli BL21 (DE3)-Codon Plus RIL as an Efficient Host. Current microbiology 13 27040822
2012 CLP36 and RIL recruit α-actinin-1 to stress fibers and differentially regulate stress fiber dynamics in F2408 fibroblasts. Experimental cell research 13 22659164
2008 Starch physicochemical properties and their associations with microsatellite alleles of starch-synthesizing genes in a rice RIL population. Journal of agricultural and food chemistry 13 18254594
2024 RIL-seq reveals extensive involvement of small RNAs in virulence and capsule regulation in hypervirulent Klebsiella pneumoniae. Nucleic acids research 12 38804271
2010 A randomized controlled multicenter study comparing recombinant interleukin 2 (rIL-2) in conjunction with recombinant interferon alpha (IFN-alpha) versus no immunotherapy for patients with malignant lymphoma postautologous stem cell transplantation. Journal of immunotherapy (Hagerstown, Md. : 1997) 12 20445353
2004 The interaction of PTP-BL PDZ domains with RIL: an enigmatic role for the RIL LIM domain. Molecular biology reports 12 15663004
2002 The associated regulators and signal pathway in rIL-16/CD4 mediated growth regulation in Jurkat cells. Cell research 12 12528894
1989 A phase II study of the administration of recombinant interleukin 2 (rIL-2) plus lymphokine activated killer (LAK) cells in stage IV melanoma patients. Tumori 12 2788945
1986 Detection of cytotoxicity of freshly obtained lymphocytes and of lymphocytes activated with recombinant interleukin II (rIL-2) against lung cancer cell lines by human tumor clonogenic assay (HTCA). European journal of cancer & clinical oncology 12 3488219
2023 Genetic linkage analysis of stable QTLs in Gossypium hirsutum RIL population revealed function of GhCesA4 in fiber development. Journal of advanced research 11 38065406
2022 Circular RNA hsa_circ_0002360 Promotes Proliferation and Invasion and Inhibits Oxidative Stress in Gastric Cancer by Sponging miR-629-3p and Regulating the PDLIM4 Expression. Oxidative medicine and cellular longevity 11 35982735
2021 Effects of the Tibetan medicine Byur dMar Nyer lNga Ril Bu on Alzheimer's disease in mice models. Journal of ethnopharmacology 11 34627984
2017 Construction of a High-Density Genetic Map from RNA-Seq Data for an Arabidopsis Bay-0 × Shahdara RIL Population. Frontiers in genetics 11 29259624
1993 Activation of the immune system of cancer patients by continuous i.v. recombinant IL-2 (rIL-2) therapy is dependent on dose and schedule of rIL-2. Clinical and experimental immunology 11 8485906
1992 Perilymphatic injections of recombinant interleukin-2 (rIL-2) partially correct the immunologic defects in patients with advanced head and neck squamous cell carcinoma. The Laryngoscope 11 1533435
1990 Purified human T cells stimulated with cross-linked anti-CD3 monoclonal antibody OKT3: rIL-1 is a co-stimulatory factor for CD4+CD29+CD45RA- T cells. Scandinavian journal of immunology 11 1700468
2020 High-density QTL mapping of leaf-related traits and chlorophyll content in three soybean RIL populations. BMC plant biology 10 33050902
2019 Mapping of barley susceptibility/resistance QTL against spot form net blotch caused by Pyrenophora teres f. maculata using RIL populations. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 10 30895332
2019 Deciphering the Genetic Architecture of Plant Height in Soybean Using Two RIL Populations Sharing a Common M8206 Parent. Plants (Basel, Switzerland) 10 31561497
2019 QTL mapping for aluminum tolerance in RIL population of soybean (Glycine max L.) by RAD sequencing. PloS one 10 31661499
2018 A consensus linkage map of lentil based on DArT markers from three RIL mapping populations. PloS one 10 29351563
2021 Identification of Main-Effect and Environmental Interaction QTL and Their Candidate Genes for Drought Tolerance in a Wheat RIL Population Between Two Elite Spring Cultivars. Frontiers in genetics 9 34220939
2021 Mapping of QTL for agronomic traits using high-density SNPs with an RIL population in maize. Genes & genomics 9 34591233
2020 PDLIM4/RIL-mediated regulation of Src and malignant properties of breast cancer cells. Oncotarget 9 32002121
2001 Phase I and II trials of subcutaneously administered rIL-2, interferon alfa-2a, and fluorouracil in patients with metastatic renal carcinoma. Journal of cancer research and clinical oncology 9 11355147