Affinage

LMO2

Rhombotin-2 · UniProt P25791

Length
158 aa
Mass
18.4 kDa
Annotated
2026-06-10
100 papers in source corpus 42 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LMO2 is a nuclear LIM-only protein that functions as an obligatory bridging scaffold within multiprotein transcription complexes governing erythroid, endothelial, and hematopoietic stem-cell programs (PMID:9214632, PMID:8033210). In erythroid cells it nucleates a pentameric DNA-binding complex with TAL1/SCL, E47/E2A, GATA-1, and LDB1/NLI that recognizes a bipartite E-box/GATA composite motif and transactivates target genes (PMID:9214632, PMID:7568177, PMID:9209374), and it likewise bridges GATA1 simultaneously with TAL1/E2A at GATA-dependent regulatory elements (PMID:21844373). Structurally, LMO2 is intrinsically disordered when newly synthesized and acquires its active conformation upon partner binding: the LID domain of LDB1 holds both LIM domains in register through a flexible hinge, and this conformational plasticity is required for SCL/TAL1 engagement and complex function (PMID:21076045, PMID:24407558, PMID:16616188). Binding of SCL strengthens the SCL:E47 heterodimer while shifting DNA contact to partner factors, defining the atomic basis for complex recruitment to hematopoietic targets (PMID:23831025), and SCL interaction additionally protects LMO2 from proteasomal degradation (PMID:17878155). Deacetylation of LMO2 on K74/K78 by the NAMPT/SIRT2 pathway is required for LDB1 engagement and complex activation (PMID:31366618). Through this complex LMO2 directly activates target genes including VE-cadherin, NRP2, ANG-2, Sphk1, Prdm16, Bcl11a, and Tcf7 to drive endothelial remodeling, hematopoietic specification, and lymphoid lineage potential (PMID:17242194, PMID:23892628, PMID:22792348, PMID:28775072, PMID:34330825, PMID:34382935), and is genetically essential for yolk-sac erythropoiesis, all adult hematopoiesis, and angiogenic vascular remodeling (PMID:8033210, PMID:9520463, PMID:10618416). LMO2 is a potent oncogene: ectopic expression drives self-renewal of immature thymocytes and T-ALL through downstream effectors HHEX and the obligate partner LYL1 (rather than SCL) (PMID:20093438, PMID:23926305, PMID:24465765). Beyond transcription, LMO2 is recruited to DNA replication origins via POLD1, PRIM1, and MCM6 to promote S-phase entry (PMID:26764384), and in DLBCL it interacts with 53BP1 to block BRCA1 recruitment, conferring homologous-recombination deficiency and PARP-inhibitor sensitivity (PMID:31447348). In solid-tumor contexts LMO2 can localize to the cytoplasm, where it binds cofilin-1 to promote migration and invasion, or DVL-1/2 to attenuate Wnt/β-catenin signaling (PMID:27880729, PMID:27779255).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 High

    Established LMO2 as a nuclear erythroid-lineage protein with a non-redundant developmental requirement, defining its biological importance before its molecular activity was known.

    Evidence Homozygous knockout in mice with in vitro yolk-sac differentiation; reciprocal Co-IP of endogenous nuclear proteins

    PMID:8033210 PMID:8078932

    Open questions at the time
    • Did not define the molecular mechanism by which LMO2 acts
    • Embryonic lethality precluded analysis of adult and other lineages
  2. 1995 High

    Identified the partner network by showing LMO2 binds GATA1/GATA2 and TAL1 and can form a quaternary complex with E47, establishing LMO2 as a multivalent protein-interaction hub.

    Evidence GST pulldown, in vivo Co-IP, and mammalian two-hybrid; plus reporter and yeast assays defining an N-terminal transactivation region and homodimerization

    PMID:7568177 PMID:7731680 PMID:9209374

    Open questions at the time
    • Did not establish DNA-binding specificity of the assembled complex
    • N-terminal transactivation function not validated in the native complex context
  3. 1997 High

    Defined the core erythroid mechanism: LMO2 bridges a pentameric TAL1/E47/GATA-1/LDB1 complex onto a bipartite E-box/GATA motif to transactivate transcription, resolving how the partners cooperate on DNA.

    Evidence Co-IP, EMSA/CASTing, mammalian two-hybrid, reporter transactivation; endogenous LDB1–LMO2 complex with overexpression differentiation readout

    PMID:9214632 PMID:9391090

    Open questions at the time
    • Did not reveal the structural basis of assembly
    • Direct endogenous target genes not yet identified
  4. 1998 High

    Showed LMO2 is cell-autonomously required for all adult hematopoietic lineages and, separately, that an oligomeric LMO2 complex recognizing a distinct double-E-box motif forms in immature thymocytes, distinguishing physiological from leukemic complexes.

    Evidence ES-cell chimera analysis with retroviral rescue; EMSA/CASTing with thymocyte subset sorting

    PMID:9520463 PMID:9707419

    Open questions at the time
    • The composition of the thymic double-E-box complex was not fully resolved
    • Did not identify downstream effectors of the leukemic complex
  5. 2000 High

    Dissected the vascular role, establishing LMO2 is dispensable for vasculogenesis but required for angiogenic remodeling of the capillary network into mature vessels.

    Evidence Chimeric mouse analysis with Lmo2-null ES cells and endothelial marker histology

    PMID:10618416

    Open questions at the time
    • Did not identify the endothelial target genes mediating remodeling
    • Mechanistic basis of the stage-specific requirement unresolved
  6. 2006 High

    Quantified LMO2–LDB1 binding, showing both LIM domains contribute and that LMO2 binds with lower affinity than LMO4, implying leukemic LDB1 sequestration is driven by elevated LMO2 levels rather than higher intrinsic affinity.

    Evidence ELISA-based affinity measurement, protein engineering, mutagenesis, yeast two-hybrid, phage display

    PMID:16616188

    Open questions at the time
    • Did not address how affinity translates into in vivo complex selectivity
    • Other LIM-domain partner affinities not compared
  7. 2007 High

    Identified the first direct endothelial target and the central role of SCL, showing the LMO2/TAL1/E47 complex occupies and activates the VE-cadherin promoter and that SCL stabilizes LMO2 from proteasomal degradation.

    Evidence siRNA, ChIP, reporter and ectopic expression; mutagenesis of the SCL interface plus proteasome inhibition and protein-stability assays

    PMID:17242194 PMID:17878155

    Open questions at the time
    • Did not define the degradation machinery acting on free LMO2
    • Generality of the stabilization mechanism across cell types not tested
  8. 2010 High

    Provided the structural and oncogenic mechanism: a 2.4 Å LMO2–LDB1 LID structure revealed LMO2 is largely unstructured and held in register by LID, with hinge flexibility required for SCL binding; in parallel, LMO2 was shown to drive thymocyte self-renewal through the downstream effector HHEX.

    Evidence X-ray crystallography with in vitro binding and in vivo rescue; lineage-tracing transgenic model with retroviral Hhex expression

    PMID:20093438 PMID:21076045

    Open questions at the time
    • Structure of the full DNA-bound complex not yet solved
    • How HHEX maintains self-renewal mechanistically not defined
  9. 2013 High

    Resolved the atomic basis of target recruitment and the obligate leukemic partner, showing the DNA-bound (SCL:E47):LMO2:LDB1 structure where LMO2 reshapes the SCL:E47 heterodimer, and that Lyl1—not Scl—is required for Lmo2's leukemic functions.

    Evidence X-ray crystallography of the pentameric DNA-bound complex; conditional double-knockout mice with human ETP-ALL cell-line validation

    PMID:23831025 PMID:23926305

    Open questions at the time
    • Why Lyl1 substitutes for Scl in leukemia at the structural level unresolved
    • Cistrome differences between Scl- and Lyl1-containing complexes not mapped
  10. 2014 High

    Reinforced the conformational-switch model with a structure of LMO2 bent at the LIM hinge by an inhibitory antibody, and identified HHEX as a direct LMO2 target genetically required for T-ALL.

    Evidence X-ray crystallography with single-domain antibody inhibition; ChIP plus conditional Hhex knockout in Lmo2-transgenic mice

    PMID:24407558 PMID:24465765

    Open questions at the time
    • The native unbound conformation in cells not directly observed
    • Full set of HHEX-dependent leukemic targets unknown
  11. 2016 High

    Extended LMO2 beyond transcription to DNA replication, showing direct binding to POLD1, PRIM1, and MCM6 recruits LMO2 to origins and is sufficient to convert synthetic sequences into replication origins driving S-phase entry.

    Evidence Co-IP, replication-origin tethering assay, shRNA with cell-cycle analysis, BrdU incorporation

    PMID:26764384

    Open questions at the time
    • How origin recruitment is coordinated with the transcriptional role unclear
    • Whether DNA binding by the complex is required for origin function not resolved
  12. 2017 High

    Defined LMO2's genome-wide cistrome role at the haemangioblast stage—positioning the TAL1/LMO2/LDB1 complex at hematopoietic regulatory elements—and identified a cytoplasmic, non-transcriptional function via cofilin-1 in invasive breast cancer.

    Evidence ChIP-seq in Lmo2-null haemangioblasts; Co-IP, fractionation, migration/invasion assays and a SCID metastasis model

    PMID:27880729 PMID:28973433

    Open questions at the time
    • Switch between nuclear scaffold and cytoplasmic cofilin functions not mechanistically defined
    • Cofilin interaction validated in a single cancer context
  13. 2019 High

    Uncovered post-translational and DNA-repair mechanisms: K74/K78 deacetylation by NAMPT/SIRT2 is required for LDB1 engagement and complex activation, and LMO2–53BP1 interaction blocks BRCA1 recruitment to confer HR deficiency and PARP-inhibitor sensitivity.

    Evidence Mass spectrometry, mutagenesis, Co-IP, NAMPT/SIRT2 inhibitor and engraftment assays; HR repair assays, BRCA1 foci and PARP-inhibitor sensitivity

    PMID:31366618 PMID:31447348

    Open questions at the time
    • The acetyltransferase that opposes SIRT2 on LMO2 not identified
    • How nuclear LMO2 is partitioned between transcription and 53BP1-bound DSBs unknown
  14. 2021 Medium

    Connected LMO2 to lineage-decision and angiogenic target genes, showing direct binding to Bcl11a/Tcf7 to maintain T-lineage potential and to prdm16 in endothelial angiogenesis, alongside an AR-repressed paracrine role in prostate cancer.

    Evidence CRISPR knockout with ChIP and rescue in pro-B cells; ChIP-PCR with zebrafish loss-of-function for prdm16; AR ChIP-seq with paracrine co-culture

    PMID:33503448 PMID:34330825 PMID:34382935

    Open questions at the time
    • Whether these targets are bound as part of the canonical pentameric complex not always defined
    • Single-lab studies awaiting independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LMO2's distinct activities—nuclear transcriptional scaffolding, replication-origin licensing, 53BP1-mediated repair inhibition, and cytoplasmic cofilin/DVL interactions—are partitioned and regulated within a single cell remains unresolved.
  • No unifying model coordinating nuclear-transcriptional, replication, repair, and cytoplasmic functions
  • Signals controlling nuclear versus cytoplasmic localization not defined
  • Acetyltransferase opposing SIRT2 and full degradation machinery for free LMO2 unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 3 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-69306 DNA Replication 1 R-HSA-73894 DNA Repair 1
Partners
53BP1DVL1E47GATA1LDB1LYL1POLD1TAL1
Complex memberships
LMO2-LDB1 complexLMO2-SAP18-HDAC1 repressor complexTAL1/SCL-E47-GATA1-LDB1 pentameric complex

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 LMO2 acts as a bridging molecule in erythroid cells, forming a pentameric DNA-binding complex with TAL1, E47 (E2A), GATA-1, and LDB1/NLI that binds a bipartite DNA motif comprising an E-box (CAGGTG) followed ~9 bp downstream by a GATA site; in vivo assembly requires all five proteins and the complex functions as a transcriptional transactivator. Co-immunoprecipitation, gel-shift/EMSA (CASTing), mammalian two-hybrid, reporter transactivation assay The EMBO journal High 9214632
1994 LMO2 (RBTN2) is a nuclear protein expressed in the erythroid lineage; homozygous knockout in mice causes complete failure of yolk sac erythropoiesis and embryonic lethality (~E10.5), demonstrating an essential role in erythroid lineage specification. Homologous recombination knockout in mice, in vitro yolk sac differentiation, double-mutant ES cell differentiation Cell High 8033210
1994 LMO2 (RBTN2) protein is not phosphorylated and forms a stable complex with the phosphoprotein TAL1 in the nucleus of erythroid cells; a similar RBTN1–TAL1 complex occurs in a T-cell leukemia line. Co-immunoprecipitation with anti-RBTN2 and anti-TAL1 antisera from nuclear extracts Proceedings of the National Academy of Sciences of the United States of America High 8078932
1995 LMO2 (RBTN2) directly interacts in vivo and in vitro with GATA1 and GATA2 zinc-finger transcription factors, as well as with TAL1; a quaternary complex of RBTN2, TAL1, GATA1, and E47 can be demonstrated by mammalian two-hybrid analysis. In vitro GST pulldown, in vivo co-immunoprecipitation, mammalian two-hybrid assay Proceedings of the National Academy of Sciences of the United States of America High 7568177 9209374
1996 LMO2 and TAL1 form protein dimers specifically in thymocytes of double-transgenic mice (not in single transgenics); co-expression of Lmo2 and Tal1 in T cells causes near-complete thymic repopulation by immature T cells from birth and accelerates T-cell tumor development by ~3 months compared to Lmo2 transgene alone, demonstrating oncogenic synergy through protein interaction. Transgenic mouse double-mutant analysis, co-immunoprecipitation from thymocytes, thymic phenotyping The EMBO journal High 8605871
1998 LMO2-null ES cells do not contribute to any hematopoietic lineage in adult chimeric mice, demonstrating LMO2 is required for all stages of adult hematopoiesis; re-introduction of an LMO2 expression vector rescues contribution to all lineages, confirming the requirement is cell-autonomous. ES cell chimera analysis, retroviral rescue experiment Proceedings of the National Academy of Sciences of the United States of America High 9520463
1997 LDB1 and LMO2 form a stable endogenous complex in erythroid cells; LDB1 and LMO2 together with SCL/E12 can assemble on SCL-binding DNA sites; forced overexpression of either LDB1 or LMO2 in proerythroblasts inhibits erythroid differentiation, indicating the LDB1/LMO2 complex maintains erythroid precursors in an immature state. Co-immunoprecipitation from MEL cells, EMSA, forced overexpression in G1ER proerythroblast cells with differentiation readout Proceedings of the National Academy of Sciences of the United States of America High 9391090
1998 In Lmo2-transgenic T cells, LMO2 forms an oligomeric DNA-binding complex that recognizes a bipartite motif of two E-box sequences ~10 bp apart (distinct from the erythroid complex), specifically in immature CD4−CD8− (double-negative) thymocytes and in T-cell tumors. EMSA (CASTing), band-shift assays, cell sorting of thymocyte subsets The EMBO journal High 9707419
2000 Lmo2-null ES cells contribute normally to the capillary network until E9, but thereafter fail to contribute to endothelial cells of large vessel walls; Lmo2 is not required for de novo vasculogenesis but is necessary for angiogenic remodeling of the existing capillary network into mature vasculature. Chimeric mouse analysis using Lmo2-null ES cells, histological and endothelial marker analysis Proceedings of the National Academy of Sciences of the United States of America High 10618416
2007 LMO2, together with TAL1 and E47, upregulates VE-cadherin transcription in endothelial cells; knockdown of LMO2 (or TAL1, E47) reduces VE-cadherin mRNA and protein; ectopic co-expression of TAL1, E47, and LMO2 activates VE-cadherin transcription in non-endothelial cells; TAL1, E47, and LMO2 occupy the VE-cadherin promoter at an E-box/GATA motif in HUVECs. siRNA knockdown, reporter assay, ectopic overexpression, chromatin immunoprecipitation Molecular and cellular biology High 17242194
2007 SCL (TAL1) is the predominant interaction partner of LMO2 in hematopoietic cells; the interaction occurs through the loop and helix-2 region of SCL; this interaction nucleates assembly of SCL complexes on DNA, is required for target gene induction and erythroid/megakaryocytic differentiation; furthermore, interaction with SCL prevents LMO2 degradation by the proteasome, thus stabilizing LMO2 protein levels. Co-immunoprecipitation, mutagenesis of SCL interaction interface, reporter/target gene induction assays, proteasome inhibitor experiments, protein stability assays The Journal of biological chemistry High 17878155
2010 Crystal structure of LMO2 in complex with the LID domain of LDB1 at 2.4 Å resolution shows LMO2 is largely unstructured and kept in register by LID binding both LIM domains; large conformational movements around a conserved hinge between the LIM domains are observed; this conformational flexibility is necessary for binding of LMO2 to SCL/TAL1 in vitro and for complex function in vivo. X-ray crystallography, in vitro binding assay, in vivo functional rescue assay, molecular docking Blood High 21076045
2013 Crystal structure of the (SCL:E47)bHLH:LMO2:LDB1LID complex bound to DNA reveals that LMO2, upon binding SCL, induces new hydrogen bonds within the SCL:E47 heterodimer strengthening it, while imposing a rotation on E47 that weakens E47:DNA contact, shifting main DNA-binding activity to additional partners; this provides the structural basis for LMO2-driven recruitment of the SCL:E47 heterodimer to hematopoietic targets. X-ray crystallography of pentameric complex, biochemical binding analyses Cell reports High 23831025
2010 LMO2 induces self-renewal of committed CD4−CD8− thymocytes more than 8 months before overt T-ALL development; these self-renewing thymocytes retain T-cell differentiation capacity but express HSC-typical genes; forced expression of HHEX (one such gene) is sufficient to initiate thymocyte self-renewal in vivo, identifying HHEX as a key downstream effector of Lmo2-induced self-renewal. Conditional cell fate mapping (lineage tracing), transgenic mouse model, retroviral overexpression of Hhex Science High 20093438
2011 The N-terminal finger of GATA1 simultaneously binds both FOG1 and LMO2; LMO2 in turn can simultaneously contact both GATA1 and SCL/TAL1 at bipartite E-box/WGATAR sites; structural data show FOG1 and TAL1/E2A/LMO2/LDB1 can co-occupy GATA1-dependent gene regulatory elements. NMR/structural analysis, binding assays, peptide competition Proceedings of the National Academy of Sciences of the United States of America High 21844373
2016 LMO2 is recruited to DNA replication origins by direct interaction with three replication enzymes—DNA polymerase delta (POLD1), DNA primase (PRIM1), and MCM6—and tethering LMO2 to synthetic sequences is sufficient to transform them into replication origins; lowering LMO2 in erythroid progenitors delays G1-S and arrests growth, while ectopic expression in thymocytes drives DNA replication and cell cycle entry. Co-immunoprecipitation, replication origin-tethering assay, shRNA knockdown with cell cycle analysis, BrdU incorporation Proceedings of the National Academy of Sciences of the United States of America High 26764384
2019 LMO2 interacts with 53BP1 during DNA double-strand break repair and thereby inhibits BRCA1 recruitment to DSBs, causing functional homologous recombination deficiency; LMO2-positive DLBCL and T-ALL cells display sensitivity to PARP inhibitors comparable to BRCA1-deficient cells. Co-immunoprecipitation (LMO2–53BP1 interaction), HR repair assays, PARP inhibitor sensitivity assays, BRCA1 recruitment foci Cancer cell High 31447348
2019 LMO2 is deacetylated on lysine residues K74 and K78 via the NAMPT/SIRT2 pathway; deacetylation is required for LMO2 to interact with LDB1 and activate the TAL1 transcriptional complex; NAMPT or SIRT2 inhibition suppresses in vitro growth and in vivo engraftment of T-ALL cells by diminishing LMO2 deacetylation. Mass spectrometry identification of acetylation sites, mutagenesis of K74/K78, Co-IP of LMO2–LDB1 interaction, NAMPT/SIRT2 inhibitor treatment, mouse engraftment assay Blood High 31366618
2014 Crystal structure of LMO2 bound to an inhibitory single-domain antibody fragment reveals a conformational change (bending at the central helical hinge between the two LIM domains) compared to the LDB1-bound form; this structural contortion sequesters LMO2 in a non-functional state, suggesting that LMO2 is intrinsically disordered when newly synthesized and adopts its active conformation upon binding a partner protein. X-ray crystallography, single-domain antibody inhibition assay Scientific reports High 24407558
2006 Both LIM domains of LMO2 are required for high-affinity binding to LDB1 (Kd ~20 nM); the first LIM domain primarily mediates this interaction while the second increases affinity ~10-fold; LMO2 binds LDB1 with ~2-fold lower affinity than does LMO4, implying that elevated LMO2 levels rather than intrinsically higher affinity drive LDB1 sequestration in leukemia. ELISA-based binding assay, protein engineering, mutagenesis, yeast two-hybrid analysis, phage display Journal of molecular biology High 16616188
2005 Human BEX2 specifically interacts with LMO2 (confirmed by GST pulldown and Co-IP) and is part of a DNA-binding complex with LMO2 as demonstrated by EMSA; BEX2 enhances LMO2 transcriptional activity in vivo; a neuronal bHLH protein NSCL2 was identified as an additional LMO2-binding partner, and LMO2 upregulates NSCL2-dependent transcription, augmented by BEX2. GST pulldown, co-immunoprecipitation, EMSA, mammalian two-hybrid, reporter assay Nucleic acids research Medium 16314316
2008 An anti-LMO2 single-chain Fv antibody binds LMO2 through its third and fourth LIM finger structures (LIM2 domain); intracellular expression inhibits Lmo2-dependent erythropoiesis but not endothelial development; it also inhibits Lmo2-dependent leukemia in a mouse T-cell tumor transplantation assay. Intracellular antibody capture technology, vector-mediated intracellular expression, erythropoiesis assay, mouse tumor transplantation assay Oncogene Medium 18438427
2013 Lmo2 requires Lyl1 (not Scl/Tal1) to mediate its leukemic functions in the thymus; Lyl1 deletion in Lmo2-transgenic mice abolishes all oncogenic functions including HSC-like gene signature upregulation, thymocyte self-renewal, and T-ALL development; Scl deletion has no effect. LMO2 and LYL1 are co-expressed in ETP-ALL patient samples and LYL1 is required for growth of ETP-ALL cell lines. Conditional double-knockout transgenic mouse model (Lmo2-Tg × Scl-cKO or Lyl1-cKO), shRNA knockdown of LYL1 in human cell lines, gene expression profiling Blood High 23926305
2003 Conditional knockout of Lmo2 using Rag1-, CD19-, or Lck-Cre drivers causes efficient Lmo2 deletion in early lymphoid progenitors but produces no disturbance of T- or B-cell lymphopoiesis, establishing that LMO2 has no mandatory role in normal T- or B-cell development. Conditional knockout mice (loxP/Cre system), flow cytometry of lymphoid populations Molecular and cellular biology High 14645513
2010 TAL1's DNA-binding activity is not required for cooperation with LMO2 in T-cell leukemia; Tal1/Lmo2 and MutTAL1/Lmo2 bitransgenic mice develop leukemia with identical kinetics; both reduce E47/HEB transcriptional activity, suggesting LMO2 cooperates with TAL1 to interfere with E47/HEB transcriptional functions rather than to activate target genes directly. Double-transgenic mouse model with DNA-binding mutant TAL1, leukemia onset comparison, E47/HEB reporter assays Oncogene Medium 21057528
1995 The NH2-terminal regions of RBTN1 and RBTN2 (LMO2) are capable of supporting transcriptional transactivation; using Isl-1 homeodomain fusions and yeast assays, the first 27 amino acids of RBTN2 are sufficient for transactivation, and RBTN2 forms homodimers in yeast. Reporter transfection assay, yeast two-hybrid assay, Isl-1 homeodomain fusion constructs Oncogene Medium 7731680
2005 LMO2 LIM2 domain deletion abolishes binding to GATA proteins (while LIM1 deletion does not); overexpression of LMO2 with mutant LIM2 but intact LIM1 causes dominant-negative inhibition of fetal hematopoiesis in transgenic mice (fetal death, small livers, decreased hematopoiesis) and inhibits DMSO-induced erythroid differentiation in MEL cells. Co-immunoprecipitation with LIM-domain deletion/mutation constructs, transgenic mouse hematopoiesis analysis, MEL cell differentiation assay Experimental hematology Medium 15911088
2017 LMO2 is required at the haemangioblast stage to position the TAL1/LMO2/LDB1 complex to regulatory elements important for establishing the haematopoietic developmental program; in the absence of LMO2, TAL1 target-site recognition genome-wide is impaired; TAL1 also sustains Lmo2 expression at this stage. Lmo2−/− ES cell differentiation to haemangioblasts, ChIP-seq (TAL1, LMO2, LDB1), genome-wide gene expression analysis, comparison with Tal1−/− cells Nucleic acids research High 28973433
2013 GATA2 and LMO2 form transcriptional complexes in endothelial cells and directly regulate neuropilin-2 (NRP2) gene expression; knockdown of either GATA2 or LMO2 inhibits VEGF-induced angiogenesis and NRP2 promoter activity; NRP2 overexpression partially rescues the knockdown phenotype. siRNA knockdown, promoter reporter assay, ChIP, angiogenesis sprouting assay, rescue by NRP2 overexpression Angiogenesis Medium 23892628
2012 Angiopoietin-2 (ANG-2) is a direct transcriptional target of LMO2, TAL1, LYL1, and GATA2 in endothelial cells; LMO2 assembles TAL1-E47, LYL1-LYL1, and/or LYL1-TAL1 dimers with GATA2 at a conserved Ebox-GATA composite element in the ANG-2 promoter; ChIP confirms occupancy of this element. siRNA knockdown, ChIP, reporter assay, ectopic co-expression in non-endothelial cells PloS one Medium 22792348
2010 c-Myb directly binds the LMO2 promoter and transactivates LMO2 expression; LMO2 (along with KLF1) overexpression partially rescues the erythroid differentiation defect caused by c-Myb silencing in human CD34+ cells. Chromatin immunoprecipitation, luciferase reporter assay, retroviral overexpression rescue, c-Myb siRNA knockdown Blood Medium 20686118
2017 Lmo2 directly regulates Sphk1 (sphingosine kinase 1) gene expression in endothelial cells by binding the Sphk1 promoter (shown by ChIP-PCR); Lmo2 KD reduces Sphk1 expression; Sphk1 mRNA rescues impaired intersegmental vessel formation and endothelial cell migration in Lmo2-KD zebrafish and human cells. Morpholino knockdown in zebrafish, siRNA in HUVECs, ChIP-PCR, scratch migration assay, mRNA rescue Arteriosclerosis, thrombosis, and vascular biology Medium 28775072
2021 Lmo2 directly binds the promoter of prdm16 in endothelial cells (shown by ChIP-PCR); lmo2 loss-of-function zebrafish mutants show reduced prdm16 expression and impaired angiogenesis; Prdm16 KD phenocopies lmo2 mutant vascular defects, defining an Lmo2–Prdm16 axis in angiogenesis. ChIP-PCR, lmo2 loss-of-function zebrafish mutants, morpholino KD, endothelial cell differentiation/migration assays Proceedings of the National Academy of Sciences of the United States of America Medium 34330825
2017 In basal-type breast cancer cells, LMO2 localizes predominantly to the cytoplasm and interacts with cofilin-1, a regulator of actin cytoskeleton dynamics; this interaction promotes tumor cell migration, invasion, and metastasis in vivo. Co-immunoprecipitation (LMO2–cofilin1), subcellular fractionation/immunofluorescence, migration/invasion assays, SCID mouse metastasis model Oncotarget Medium 27880729
2016 In breast and colorectal cancer cells, LMO2 localizes to the cytoplasm and binds to the PDZ domain of Dishevelled-1/2 (DVL-1/2); this interaction attenuates canonical Wnt/β-catenin signaling; LMO2 downregulation increases cell proliferation and reduces apoptosis in these cells. Co-immunoprecipitation (LMO2–DVL1/2), β-catenin activity assay, LMO2 overexpression and knockdown with proliferation/apoptosis readouts Scientific reports Medium 27779255
2018 LMO2 recruits SAP18 and HDAC1 to form an epigenetic regulatory complex on the ZEB1 promoter, inducing histone deacetylation and transcriptional repression of ZEB1; ZEB1 downregulation increases leukemia stem cell phenotype and reduces sensitivity to methotrexate in T-ALL; HDAC inhibitor TSA restores chemosensitivity. Co-immunoprecipitation (LMO2–SAP18–HDAC1), ChIP at ZEB1 promoter, HDAC inhibitor treatment, shRNA knockdown, leukemia stem cell assays Biochimica et biophysica acta. Molecular basis of disease Medium 29778661
2021 LMO2 directly binds the Bcl11a and Tcf7 loci in pro-B cells; LMO2 is required to maintain T-lineage potential in pre-thymic progenitors; CRISPR/Cas9 deletion of Lmo2 abolishes T-lineage potential; ectopic Lmo2 expression restores this potential by enabling Bcl11a and Tcf7 expression. CRISPR/Cas9 knockout, ChIP (LMO2 at Bcl11a and Tcf7 loci), ectopic expression rescue, in vitro T-cell differentiation assay eLife Medium 34382935
2014 HHEX is a direct transcriptional target of LMO2 in T-ALL; conditional inactivation of Hhex in CD2-Lmo2 transgenic mice markedly attenuates T-ALL development, establishing HHEX as a crucial mediator of Lmo2's oncogenic function. ChIP (LMO2 at HHEX locus), conditional Hhex knockout in Lmo2-transgenic mice, T-ALL incidence analysis PloS one Medium 24465765
2009 miR-223 binds the 3' UTR of LMO2 and reduces LMO2 mRNA and protein levels; enforced expression of miR-223 impairs erythroid differentiation, phenocopied by LMO2 siRNA knockdown; the decline of miR-223 during erythropoiesis is required to allow LMO2 upregulation and erythroid commitment. 3' UTR luciferase reporter assay, miR-223 overexpression, LMO2 siRNA knockdown, erythroid colony assay Haematologica Medium 19278969
2005 The LMO2 proximal promoter is active in hematopoietic progenitor and endothelial cell lines in a manner dependent on three conserved ETS-binding sites bound in vivo by ELF1, FLI1, and ETS1; transgenic analysis confirms the proximal promoter drives expression in endothelial cells in vivo but additional enhancers are needed for hematopoietic expression. Comparative genomics, transient and stable transfections, ChIP, transgenic mouse analysis Blood Medium 15994290
2021 LMO2 is identified as an AR (androgen receptor) target gene in prostate fibroblasts; AR directly represses LMO2 through binding to androgen response elements (AREs) in the LMO2 locus (ChIP-seq); upon AR deactivation, LMO2 overexpression in fibroblasts promotes castration-resistant PCa cell growth non-cell-autonomously via paracrine IL-11 and FGF-9. ChIP-seq (AR binding at LMO2 locus), LMO2 knockdown and overexpression, paracrine co-culture experiments, cytokine neutralization Cancer letters Medium 33503448

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science (New York, N.Y.) 2787 14564000
1997 The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins. The EMBO journal 737 9214632
1994 The oncogenic cysteine-rich LIM domain protein rbtn2 is essential for erythroid development. Cell 540 8033210
1991 TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukaemia with the t(11;14)(p13;q11). Oncogene 258 1923511
1998 The T cell leukemia LIM protein Lmo2 is necessary for adult mouse hematopoiesis. Proceedings of the National Academy of Sciences of the United States of America 254 9520463
1994 The LIM protein RBTN2 and the basic helix-loop-helix protein TAL1 are present in a complex in erythroid cells. Proceedings of the National Academy of Sciences of the United States of America 205 8078932
2010 The Lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal. Science (New York, N.Y.) 192 20093438
1996 Protein dimerization between Lmo2 (Rbtn2) and Tal1 alters thymocyte development and potentiates T cell tumorigenesis in transgenic mice. The EMBO journal 178 8605871
1995 Association of erythroid transcription factors: complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1. Proceedings of the National Academy of Sciences of the United States of America 177 7568177
2000 The oncogenic LIM-only transcription factor Lmo2 regulates angiogenesis but not vasculogenesis in mice. Proceedings of the National Academy of Sciences of the United States of America 147 10618416
2003 Lmo2 and Scl/Tal1 convert non-axial mesoderm into haemangioblasts which differentiate into endothelial cells in the absence of Gata1. Development (Cambridge, England) 142 14602685
1997 The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation. Proceedings of the National Academy of Sciences of the United States of America 138 9391090
2006 The oncoprotein LMO2 is expressed in normal germinal-center B cells and in human B-cell lymphomas. Blood 135 17038524
2009 MicroRNA 223-dependent expression of LMO2 regulates normal erythropoiesis. Haematologica 120 19278969
2006 The transcription factors Scl and Lmo2 act together during development of the hemangioblast in zebrafish. Blood 118 17090656
2003 The LMO2 T-cell oncogene is activated via chromosomal translocations or retroviral insertion during gene therapy but has no mandatory role in normal T-cell development. Molecular and cellular biology 117 14645513
1992 T-cell acute lymphoblastic lymphoma induced in transgenic mice by the RBTN1 and RBTN2 LIM-domain genes. Oncogene 112 1461647
2017 A Grapevine TTG2-Like WRKY Transcription Factor Is Involved in Regulating Vacuolar Transport and Flavonoid Biosynthesis. Frontiers in plant science 99 28105033
2005 The role of LMO2 in development and in T cell leukemia after chromosomal translocation or retroviral insertion. Molecular therapy : the journal of the American Society of Gene Therapy 95 16260184
1998 The oncogenic T cell LIM-protein Lmo2 forms part of a DNA-binding complex specifically in immature T cells. The EMBO journal 94 9707419
2010 c-myb supports erythropoiesis through the transactivation of KLF1 and LMO2 expression. Blood 93 20686118
2010 A self-inactivating lentiviral vector for SCID-X1 gene therapy that does not activate LMO2 expression in human T cells. Blood 91 20457870
2010 miR-223 and miR-142 attenuate hematopoietic cell proliferation, and miR-223 positively regulates miR-142 through LMO2 isoforms and CEBP-β. Cell research 87 20856265
2000 Lmo2 and GATA-3 associated expression in intraembryonic hemogenic sites. Development (Cambridge, England) 86 10631184
1994 T cell tumours of disparate phenotype in mice transgenic for Rbtn-2. Oncogene 86 7970726
2005 Regulation of the lmo2 promoter during hematopoietic and vascular development in zebrafish. Developmental biology 82 15893977
1997 Defects of the mismatch repair gene MSH2 are implicated in the development of murine and human lymphoblastic lymphomas and are associated with the aberrant expression of rhombotin-2 (Lmo-2) and Tal-1 (SCL). Blood 82 9116269
1995 The oncogenic LIM protein Rbtn2 causes thymic developmental aberrations that precede malignancy in transgenic mice. Oncogene 78 7545805
2017 Activation of the LMO2 oncogene through a somatically acquired neomorphic promoter in T-cell acute lymphoblastic leukemia. Blood 68 28270453
2009 Expression of the leukemia oncogene Lmo2 is controlled by an array of tissue-specific elements dispersed over 100 kb and bound by Tal1/Lmo2, Ets, and Gata factors. Blood 66 19171877
2007 TAL-1/SCL and its partners E47 and LMO2 up-regulate VE-cadherin expression in endothelial cells. Molecular and cellular biology 66 17242194
2019 LMO2 Confers Synthetic Lethality to PARP Inhibition in DLBCL. Cancer cell 64 31447348
2015 LMO2 at 25 years: a paradigm of chromosomal translocation proteins. Open biology 60 26108219
2013 Requirement for Lyl1 in a model of Lmo2-driven early T-cell precursor ALL. Blood 60 23926305
2010 Structure of the leukemia oncogene LMO2: implications for the assembly of a hematopoietic transcription factor complex. Blood 60 21076045
2013 Structural basis for LMO2-driven recruitment of the SCL:E47bHLH heterodimer to hematopoietic-specific transcriptional targets. Cell reports 57 23831025
2014 LIM domain only-2 (LMO2) induces T-cell leukemia by two distinct pathways. PloS one 51 24465765
2005 Fli1, Elf1, and Ets1 regulate the proximal promoter of the LMO2 gene in endothelial cells. Blood 51 15994290
2007 The significance of LMO2 expression in the progression of prostate cancer. The Journal of pathology 48 17167821
2013 GATA2 and Lmo2 control angiogenesis and lymphangiogenesis via direct transcriptional regulation of neuropilin-2. Angiogenesis 47 23892628
1999 The effect of chromosomal translocations in acute leukemias: the LMO2 paradigm in transcription and development. Cancer research 47 10197599
2013 Lmo2 induces hematopoietic stem cell-like features in T-cell progenitor cells prior to leukemia. Stem cells (Dayton, Ohio) 46 23378057
1997 Expression of LIM protein genes Lmo1, Lmo2, and Lmo3 in adult mouse hippocampus and other forebrain regions: differential regulation by seizure activity. The Journal of neuroscience : the official journal of the Society for Neuroscience 45 9204936
2002 The LIM-domain protein Lmo2 is a key regulator of tumour angiogenesis: a new anti-angiogenesis drug target. Oncogene 44 11857074
2015 The LIM-only transcription factor LMO2 determines tumorigenic and angiogenic traits in glioma stem cells. Cell death and differentiation 41 25721045
2011 Structural basis of simultaneous recruitment of the transcriptional regulators LMO2 and FOG1/ZFPM1 by the transcription factor GATA1. Proceedings of the National Academy of Sciences of the United States of America 41 21844373
2015 Expression of Brassica napus TTG2, a regulator of trichome development, increases plant sensitivity to salt stress by suppressing the expression of auxin biosynthesis genes. Journal of experimental botany 39 26071533
2008 An antibody inhibitor of the LMO2-protein complex blocks its normal and tumorigenic functions. Oncogene 38 18438427
1995 The TTG-2/RBTN2 T cell oncogene encodes two alternative transcripts from two promoters: the distal promoter is removed by most 11p13 translocations in acute T cell leukaemia's (T-ALL). Oncogene 37 7731686
2009 Targeting LMO2 with a peptide aptamer establishes a necessary function in overt T-cell neoplasia. Cancer research 36 19487290
2010 A previously unrecognized promoter of LMO2 forms part of a transcriptional regulatory circuit mediating LMO2 expression in a subset of T-acute lymphoblastic leukaemia patients. Oncogene 35 20676125
2010 Immunoarchitectural patterns in follicular lymphoma: efficacy of HGAL and LMO2 in the detection of the interfollicular and diffuse components. The American journal of surgical pathology 35 20697248
2007 Protein stability and transcription factor complex assembly determined by the SCL-LMO2 interaction. The Journal of biological chemistry 35 17878155
2005 Human Bex2 interacts with LMO2 and regulates the transcriptional activity of a novel DNA-binding complex. Nucleic acids research 35 16314316
2018 Lmo2 expression defines tumor cell identity during T-cell leukemogenesis. The EMBO journal 34 29880602
2010 Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17;19). Blood 34 20519628
2012 Detection of LIM domain only 2 (LMO2) in normal human tissues and haematopoietic and non-haematopoietic tumours using a newly developed rabbit monoclonal antibody. Histopathology 33 22394247
2010 The molecular basis of Lmo2-induced T-cell acute lymphoblastic leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research 33 20861166
2010 The E2A-HLF oncogenic fusion protein acts through Lmo2 and Bcl-2 to immortalize hematopoietic progenitors. Leukemia 33 21072044
2017 LMO2 promotes tumor cell invasion and metastasis in basal-type breast cancer by altering actin cytoskeleton remodeling. Oncotarget 30 27880729
2016 LMO2 attenuates tumor growth by targeting the Wnt signaling pathway in breast and colorectal cancer. Scientific reports 30 27779255
2015 Diagnostic Utility of the Germinal Center-associated Markers GCET1, HGAL, and LMO2 in Hematolymphoid Neoplasms. Applied immunohistochemistry & molecular morphology : AIMM 30 25203428
2010 A DNA-binding mutant of TAL1 cooperates with LMO2 to cause T cell leukemia in mice. Oncogene 30 21057528
2011 LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome. Haematologica 29 21459790
2011 Characterization of a pediatric T-cell acute lymphoblastic leukemia patient with simultaneous LYL1 and LMO2 rearrangements. Haematologica 29 22058201
2006 Identification of the key LMO2-binding determinants on Ldb1. Journal of molecular biology 29 16616188
2014 LMO2 and BCL6 are associated with improved survival in primary central nervous system lymphoma. British journal of haematology 28 24571259
2009 The transcription factor LMO2 is a robust marker of vascular endothelium and vascular neoplasms and selected other entities. American journal of clinical pathology 28 19141387
2016 The LMO2 oncogene regulates DNA replication in hematopoietic cells. Proceedings of the National Academy of Sciences of the United States of America 27 26764384
2008 Functional characterization of Lmo2-Cre transgenic zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists 26 18627109
2011 Functional interactions between Lmo2, the Arf tumor suppressor, and Notch1 in murine T-cell malignancies. Blood 25 21427293
2003 A PAR domain transcription factor is involved in the expression from a hematopoietic-specific promoter for the human LMO2 gene. Blood 25 12609830
2019 ZEB2 and LMO2 drive immature T-cell lymphoblastic leukemia via distinct oncogenic mechanisms. Haematologica 24 30679322
2017 LMO2-negative Expression Predicts the Presence of MYC Translocations in Aggressive B-Cell Lymphomas. The American journal of surgical pathology 24 28288039
2008 Assembly of the oncogenic DNA-binding complex LMO2-Ldb1-TAL1-E12. Proteins 24 17910069
2017 Lmo2 (LIM-Domain-Only 2) Modulates Sphk1 (Sphingosine Kinase) and Promotes Endothelial Cell Migration. Arteriosclerosis, thrombosis, and vascular biology 23 28775072
2016 LMO2 Is a Specific Marker of T-Lymphoblastic Leukemia/Lymphoma. American journal of clinical pathology 23 26796495
1997 LIM-only protein Lmo2 forms a protein complex with erythroid transcription factor GATA-1. Leukemia 23 9209374
2012 Angiopoietin-2 is a direct transcriptional target of TAL1, LYL1 and LMO2 in endothelial cells. PloS one 22 22792348
2019 LMO2 activation by deacetylation is indispensable for hematopoiesis and T-ALL leukemogenesis. Blood 21 31366618
2005 SCL, GATA-2 and Lmo2 expression in neurogenesis. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 21 16011889
2017 LMO2 is required for TAL1 DNA binding activity and initiation of definitive haematopoiesis at the haemangioblast stage. Nucleic acids research 20 28973433
2011 The efficacy of HGAL and LMO2 in the separation of lymphomas derived from small B cells in nodal and extranodal sites, including the bone marrow. American journal of clinical pathology 20 21502424
1995 Functional diversity of LIM proteins: amino-terminal activation domains in the oncogenic proteins RBTN1 and RBTN2. Oncogene 20 7731680
2014 Hhex regulates Kit to promote radioresistance of self-renewing thymocytes in Lmo2-transgenic mice. Leukemia 19 25283843
2013 TTG2-regulated development is related to expression of putative AUXIN RESPONSE FACTOR genes in tobacco. BMC genomics 19 24252253
2012 Tobacco TTG2 suppresses resistance to pathogens by sequestering NPR1 from the nucleus. Journal of cell science 19 22797922
2005 Transcriptional control of fetal liver hematopoiesis: dominant negative effect of the overexpression of the LIM domain mutants of LMO2. Experimental hematology 19 15911088
2021 LMO2 upregulation due to AR deactivation in cancer-associated fibroblasts induces non-cell-autonomous growth of prostate cancer after androgen deprivation. Cancer letters 18 33503448
2020 TOP1α, UPF1, and TTG2 regulate seed size in a parental dosage-dependent manner. PLoS biology 18 33156841
2022 Endothelial versus pronephron fate decision is modulated by the transcription factors Cloche/Npas4l, Tal1, and Lmo2. Science advances 17 36044573
2021 Fli1+ cells transcriptional analysis reveals an Lmo2-Prdm16 axis in angiogenesis. Proceedings of the National Academy of Sciences of the United States of America 17 34330825
2016 Tobacco TTG2 regulates vegetative growth and seed production via the predominant role of ARF8 in cooperation with ARF17 and ARF19. BMC plant biology 17 27255279
2021 LMO2 is essential to maintain the ability of progenitors to differentiate into T-cell lineage in mice. eLife 16 34382935
2018 Epigenetic dysregulation of ZEB1 is involved in LMO2-promoted T-cell acute lymphoblastic leukaemia leukaemogenesis. Biochimica et biophysica acta. Molecular basis of disease 16 29778661
2017 Diagnostic value of STMN1, LMO2, HGAL, AID expression and 1p36 chromosomal abnormalities in primary cutaneous B cell lymphomas. Histopathology 16 28594133
2015 BCL6--regulated by AhR/ARNT and wild-type MEF2B--drives expression of germinal center markers MYBL1 and LMO2. Haematologica 16 25769544
2014 Conformational flexibility of the oncogenic protein LMO2 primes the formation of the multi-protein transcription complex. Scientific reports 16 24407558
1994 Simultaneous expression of RBTN-2 and BCR-ABL oncogenes in a T-ALL with a t(11;14)(p13;q11) and a late-appearing Philadelphia chromosome. Leukemia 16 8035604
1992 Rhom-2 expression does not always correlate with abnormalities on chromosome 11 at band p13 in T-cell acute lymphoblastic leukemia. Blood 16 1281693

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