Affinage

LMO2

Rhombotin-2 · UniProt P25791

Length
158 aa
Mass
18.4 kDa
Annotated
2026-04-28
100 papers in source corpus 40 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LMO2 is a LIM-only transcriptional scaffolding protein essential for definitive hematopoiesis, erythropoiesis, and angiogenic vascular remodeling. It functions as an intrinsically disordered bridge that is stabilized upon binding LDB1 via its LIM domains; this interaction is regulated by SIRT2-mediated deacetylation of Lys74/78 and by SCL/TAL1 binding, which prevents proteasomal degradation (PMID:21076045, PMID:31366618, PMID:17878155). LMO2 nucleates distinct multiprotein DNA-binding complexes—containing TAL1 or LYL1 with E-proteins, GATA factors, and LDB1—at E-box/GATA composite elements to activate hematopoietic (e.g., HHEX) and endothelial (e.g., ANG-2, NRP2, SPHK1) gene programs, and is required genome-wide for TAL1 chromatin occupancy (PMID:28973433, PMID:22792348, PMID:24465765). Beyond transcription, LMO2 directly promotes DNA replication by interacting with POLD1, PRIM1, and MCM6 at origins (PMID:26764384), and in DLBCL it impairs homologous recombination by sequestering 53BP1 from BRCA1 at double-strand breaks, conferring PARP-inhibitor sensitivity (PMID:31447348).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1994 High

    Loss-of-function established LMO2 as indispensable for primitive erythropoiesis, answering whether this T-ALL translocation target had a normal developmental role.

    Evidence Homologous recombination knockout in mice causing embryonic lethal failure of yolk sac erythropoiesis

    PMID:8033210

    Open questions at the time
    • Mechanism of action (transcription factor? cofactor?) unknown
    • Role in definitive hematopoiesis not yet tested
    • Downstream targets unidentified
  2. 1994 High

    Identification of the LMO2–TAL1 physical complex in erythroid cells provided the first evidence that two T-ALL oncogenes cooperate through direct protein interaction in normal hematopoiesis.

    Evidence Reciprocal co-immunoprecipitation in erythroid cell lines

    PMID:8078932

    Open questions at the time
    • Stoichiometry and additional complex members unknown
    • DNA binding of the complex not demonstrated
  3. 1995 High

    Discovery that LMO2 bridges TAL1 to GATA1/GATA2 and E47 defined the multiprotein architecture through which LMO2 links hematopoietic transcription factors on DNA.

    Evidence In vitro pull-down, co-IP, and mammalian two-hybrid

    PMID:7568177 PMID:9209374

    Open questions at the time
    • 3D structure of the complex unknown
    • Direct DNA target genes not identified
  4. 1996 High

    Demonstration that LMO2 and TAL1 synergize to accelerate T-cell leukemia in vivo established the oncogenic mechanism as a physical protein dimer in thymocytes.

    Evidence Double-transgenic mice with protein dimerization detection and tumor latency comparison

    PMID:8605871

    Open questions at the time
    • Identity of the critical partner in T-ALL (TAL1 vs. LYL1) not resolved
    • Downstream oncogenic transcriptional targets unknown
  5. 1997 High

    Identification of LDB1 as a stable partner of LMO2 added the fourth core subunit to the hematopoietic complex and showed that this complex maintains erythroid precursors in an immature state.

    Evidence Co-IP in murine erythroleukemia cells, EMSA, and forced expression in proerythroblasts

    PMID:9391090

    Open questions at the time
    • Structural basis of LMO2–LDB1 interaction unknown
    • How complex stoichiometry is regulated unclear
  6. 1998 High

    Chimeric mouse experiments proved LMO2 is required for all adult hematopoietic lineages, not just primitive erythropoiesis, and that this requirement could be rescued by transgene re-expression.

    Evidence Lmo2-null ES cell chimeras with retroviral rescue

    PMID:9520463

    Open questions at the time
    • Whether LMO2 acts at the level of HSC self-renewal or differentiation unclear
    • Cell-type-specific complex composition not explored
  7. 2000 High

    Establishing that LMO2 is required for angiogenic remodeling but not de novo vasculogenesis extended its function beyond blood to endothelium.

    Evidence Lmo2-null ES cell chimeras with vascular phenotyping

    PMID:10618416

    Open questions at the time
    • Endothelial target genes of LMO2 unknown
    • Whether the same TAL1-containing complex operates in endothelium unclear
  8. 2003 High

    NMR structure of LMO2:LDB1-LID provided the first atomic-resolution view of how LDB1 binds as an extended strand to the LIM1 domain, revealing the structural basis of the core scaffolding interaction.

    Evidence NMR structure determination

    PMID:12727888

    Open questions at the time
    • Full pentameric complex structure on DNA not available
    • Conformational dynamics between LIM domains uncharacterized
  9. 2010 High

    The crystal structure of LMO2:LDB1 revealed that LMO2 is largely intrinsically disordered and requires LDB1 to adopt a defined conformation, with a flexible hinge between LIM domains critical for TAL1 binding and in vivo function.

    Evidence X-ray crystallography at 2.4 Å with mutant rescue in zebrafish

    PMID:21076045

    Open questions at the time
    • Hinge dynamics in solution not measured
    • How disorder-to-order transition is regulated in the cell unknown
  10. 2011 High

    Structural demonstration that GATA1 simultaneously contacts LMO2 and FOG1 resolved how FOG1-dependent and TAL1/LMO2-dependent gene regulation can co-occur at the same GATA1-bound sites.

    Evidence NMR structure, EMSA, and pulldown assays

    PMID:21844373

    Open questions at the time
    • Genome-wide co-occupancy of FOG1 and LMO2 complex not mapped
    • Whether this dual binding mode operates at all GATA1 targets unclear
  11. 2012 High

    Identification of an LMO2–TAL1/LYL1–GATA2 complex at the ANG-2 promoter in endothelial cells demonstrated a direct endothelial transcriptional target and showed the hematopoietic-type complex operates in vasculature.

    Evidence ChIP at endogenous ANG-2 promoter with siRNA knockdown of each factor

    PMID:22792348

    Open questions at the time
    • Genome-wide endothelial target repertoire not defined
    • Complex composition may differ across vascular beds
  12. 2013 High

    The crystal structure of the full (SCL:E47)bHLH:LMO2:LDB1 complex on DNA revealed that LMO2 allosterically strengthens the SCL:E47 heterodimer while rotating E47 to weaken its DNA grip, explaining how LMO2 shifts DNA-binding specificity.

    Evidence X-ray crystallography of multiprotein–DNA complex with biochemical validation

    PMID:23831025

    Open questions at the time
    • Whether this allosteric mechanism applies to LYL1-containing complexes unknown
    • In vivo consequences of the rotational shift not directly tested
  13. 2013 High

    Genetic epistasis showed that LYL1, not SCL/TAL1, is the obligate bHLH partner recruited by LMO2 to drive T-cell leukemia, resolving a longstanding ambiguity about the oncogenic complex composition.

    Evidence Conditional knockout of Scl or Lyl1 in Lmo2-transgenic mice with transplantation and gene expression profiling

    PMID:23926305

    Open questions at the time
    • How LMO2 selects LYL1 over TAL1 in thymocytes not mechanistically explained
    • Direct LYL1:LMO2 binding affinity not measured
  14. 2016 High

    Discovery that LMO2 interacts with replication machinery (POLD1, PRIM1, MCM6) and can convert arbitrary DNA into a replication origin revealed an unexpected non-transcriptional function in DNA replication initiation.

    Evidence Co-IP with replication enzymes, synthetic origin tethering assay, BrdU incorporation, ChIP at origins

    PMID:26764384

    Open questions at the time
    • Whether replication function is separable from transcriptional function in vivo unclear
    • Structural basis of LMO2–replication machinery interaction unknown
    • Relevance to normal vs. oncogenic replication programs not delineated
  15. 2017 High

    Genome-wide ChIP-seq in Lmo2-knockout cells proved that LMO2 is required for TAL1 chromatin occupancy at hematopoietic regulatory elements, establishing LMO2 as a positioning factor rather than a passive scaffold.

    Evidence Lmo2−/− ES cell differentiation with genome-wide TAL1 and LMO2 ChIP-seq

    PMID:28973433

    Open questions at the time
    • Mechanism by which LMO2 enables TAL1 DNA binding (chromatin opening vs. direct tethering) not resolved
  16. 2019 High

    LMO2 was shown to impair homologous recombination by sequestering 53BP1 from BRCA1 at DSBs, providing a non-transcriptional mechanism for its role in DLBCL biology and creating a therapeutic vulnerability to PARP inhibitors.

    Evidence Co-IP of LMO2 with 53BP1, BRCA1 recruitment assay, HR functional assay, PARP inhibitor sensitivity in DLBCL and T-ALL cells

    PMID:31447348

    Open questions at the time
    • Whether the LMO2–53BP1 interaction is direct or bridged unknown
    • Structural details of the interaction not available
    • Clinical efficacy of PARP inhibitors in LMO2-expressing tumors not established
  17. 2019 High

    Identification of SIRT2-mediated deacetylation of LMO2 at K74/K78 as a prerequisite for LDB1 binding revealed the first post-translational regulatory switch controlling LMO2 complex assembly.

    Evidence Mass spectrometry acetylation mapping, SIRT2 deacetylase assay, Co-IP of deacetylated LMO2 with LDB1, NAMPT/SIRT2 inhibitor treatment, zebrafish assay

    PMID:31366618

    Open questions at the time
    • Which acetyltransferase acetylates LMO2 not identified
    • Whether acetylation state also regulates replication or DNA repair functions unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LMO2's transcriptional, replication-initiating, and DNA-repair-inhibitory functions are coordinated or partitioned across cell types and cell-cycle phases remains unresolved.
  • No integrative study has tested all three functions in the same cell system
  • Structural basis for LMO2 interaction with replication machinery and 53BP1 lacking
  • Whether LMO2 post-translational modifications differentially regulate each function is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0140110 transcription regulator activity 5
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-69306 DNA Replication 1 R-HSA-73894 DNA Repair 1
Partners
53BP1GATA1GATA2LDB1LYL1POLD1PRIM1TAL1
Complex memberships
GATA1/2–LMO2–TAL1–E47–LDB1 complexLYL1–E2A–LMO2–LDB1 complexTAL1/SCL–E47–LMO2–LDB1 complex

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 LMO2 (RBTN2) is a nuclear protein essential for yolk sac erythropoiesis; homologous recombination knockout in mice causes failure of erythroid development and embryonic lethality around E10.5, establishing its pivotal role in lineage specification. Homologous recombination knockout in mice, in vitro differentiation of yolk sac tissue, ES cell targeting Cell High 8033210
1994 LMO2 (RBTN2) forms a complex with TAL1 in the nucleus of erythroid cells; RBTN2 is not phosphorylated while TAL1 is a phosphoprotein; both proteins are coexpressed in erythroid cells and are crucial for erythropoiesis. Co-immunoprecipitation with anti-RBTN2 and anti-TAL1 antisera in erythroid cells 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; mammalian two-hybrid analysis demonstrated a complex involving RBTN2, TAL1, GATA1, and E47, linking three proteins crucial for erythropoiesis. In vitro pull-down, co-immunoprecipitation, mammalian two-hybrid analysis Proceedings of the National Academy of Sciences of the United States of America High 7568177 9209374
1996 LMO2 and TAL1 proteins form dimers in thymocytes of double-transgenic mice; co-expression of Lmo2 and Tal1 in T cells alters thymocyte development (accumulation of immature T cells) and potentiates T-cell tumor formation approximately 3 months earlier than Lmo2 alone, demonstrating synergistic oncogenic interaction. Transgenic mouse co-expression, protein dimerization detection in thymocytes, tumor latency comparison The EMBO journal High 8605871
1997 LMO2 and Ldb1 exist in a stable complex in murine erythroleukemia cells; Ldb1, LMO2, and SCL/E12 can assemble as a multiprotein complex on a consensus SCL binding site; forced expression of Ldb1 or LMO2 in erythroid progenitor cells inhibits cellular maturation, indicating LMO2-Ldb1 complex maintains erythroid precursors in an immature state. Co-immunoprecipitation, gel shift/EMSA, forced expression in G1ER proerythroblast cells Proceedings of the National Academy of Sciences of the United States of America High 9391090
1998 Lmo2 null ES cells do not contribute to any hematopoietic lineage in adult chimeric mice, demonstrating Lmo2 is necessary for all adult hematopoiesis; reintroduction of Lmo2 expression vector rescues this defect, and the mechanism likely involves interaction with Tal1/Scl. Chimeric mouse assay with homozygous Lmo2-/- ES cells, rescue by retroviral re-expression Proceedings of the National Academy of Sciences of the United States of America High 9520463
1998 In T cells from Lmo2 transgenic mice, Lmo2 forms an oligomeric DNA-binding complex that recognizes a bipartite motif of two E-box sequences ~10 bp apart; this complex is restricted to immature CD4-CD8- thymocytes and is distinct from the complex found in erythroid cells. CASTing (cyclic amplification and selection of targets), band shift/EMSA, immunophenotyping The EMBO journal High 9707419
2000 Lmo2 is expressed in vascular endothelium and is required for angiogenic remodeling of the capillary network into mature vasculature but not for de novo vasculogenesis; Lmo2-null ES cells fail to contribute to endothelial cells of large vessel walls after E10, demonstrating a distinct role in angiogenesis. Chimeric mouse analysis with Lmo2-null ES cells, histological and vascular imaging Proceedings of the National Academy of Sciences of the United States of America High 10618416
2001 In Xenopus, LMO-2 acts synergistically with SCL and GATA-1 to specify hematopoietic mesoderm; co-expression of all three factors leads to ventralized embryos with ectopic blood, and their interaction in a transcriptional complex was demonstrated in vitro. Xenopus animal cap assay, whole embryo overexpression, in vitro complex assembly Development (Cambridge, England) High 11493549
2002 Lmo2 is an obligatory regulator of tumor neo-vascularization; Lmo2-null ES cells fail to produce CD31-positive sprouting endothelium in teratocarcinomas in nude mice, while heterozygous cells do, establishing Lmo2 as necessary for tumor angiogenesis. Teratocarcinoma model in nude mice using Lmo2-null and heterozygous ES cells, CD31 immunostaining Oncogene High 11857074
2003 The solution structures of LMO2:ldb1 and LMO4:ldb1 complexes were determined by NMR; ldb1-LID binds to the N-terminal LIM domain (LIM1) of LMO2 in an extended conformation, contributing a third strand to a beta-hairpin in LIM1, providing the first molecular definition of LIM-mediated protein-protein interactions. NMR structure determination (PDB: 1M3V and 1J2O) The EMBO journal High 12727888
2005 The LMO2 proximal promoter is regulated by ETS transcription factors Elf1, Fli1, and Ets1, which bind to three conserved ETS sites in vivo; this promoter is sufficient for endothelial expression in vivo but requires additional enhancers for hematopoietic expression. Chromatin immunoprecipitation, transient/stable transfection, transgenic mouse analysis Blood High 15994290
2006 Scl and Lmo2 act together in zebrafish hemangioblast development; scl morphants cannot be rescued by a non-Lmo2-binding form of Scl but can be rescued by non-DNA-binding forms, indicating Scl is tethered to target genes through DNA-binding partners via Lmo2. Zebrafish morpholino knockdown, rescue with mutant Scl constructs, epistasis analysis Blood High 17090656
2007 LMO2 and SCL interact through a conserved interface in the SCL loop and helix 2; this interaction nucleates assembly of SCL complexes on DNA, is required for target gene induction and erythroid/megakaryocytic differentiation, and SCL prevents LMO2 degradation by the proteasome. Co-immunoprecipitation, domain mutagenesis, in vitro binding assays, proteasome inhibitor experiments The Journal of biological chemistry High 17878155
2008 The oncogenic LMO2-Ldb1-TAL1-E12 complex was characterized biophysically; TAL1/E12 bHLH preferentially form heterodimers to which LMO2 binds with high affinity (~10^8 M^-1); the resulting complex forms in the presence or absence of DNA and preferentially binds different E-box sequences. Biophysical characterization (analytical ultracentrifugation, ITC), EMSA Proteins High 17910069
2008 An anti-LMO2 single-chain Fv antibody specific for the LIM3-LIM4 region of LMO2 inhibits Lmo2-dependent erythropoiesis and prevents Lmo2-dependent leukemia in a mouse transplantation assay, demonstrating that interference with the LMO2 multiprotein complex disrupts both normal and tumorigenic roles. Intracellular antibody capture, vector-mediated scFv expression, mouse T-cell tumor transplantation assay Oncogene High 18438427
2009 miR-223 directly binds the LMO2 3' UTR to reduce LMO2 mRNA and protein levels; enforced miR-223 expression impairs erythroid differentiation, and LMO2 knockdown by siRNA mimics this effect, establishing miR-223 as a negative post-transcriptional regulator of LMO2 during erythropoiesis. 3'UTR reporter assay, siRNA knockdown, forced miRNA expression in CD34+ progenitors, clonogenic assay Haematologica High 19278969
2009 LMO2 expression is controlled by an array of tissue-specific regulatory elements spread over >100 kb; Sfpi1/Pu.1, Fli1, Gata2, Tal1/Scl, and Lmo2 itself bind to and transactivate Lmo2 hematopoietic enhancers, placing Lmo2 within an autoregulatory hematopoietic network. Comparative genomics, ChIP-chip across 250 kb locus in 11 cell types, transgenic mouse enhancer assays Blood High 19171877
2010 The crystal structure of LMO2 in complex with the LDB1-LID domain was solved at 2.4 Å; LMO2 is largely unstructured and kept in register by LID binding both LIM domains; conformational flexibility around a conserved hinge is necessary for binding to SCL/TAL1 in vitro and for function in vivo. X-ray crystallography at 2.4 Å, in vitro binding assays, in vivo functional rescue Blood High 21076045
2010 c-Myb binds to the LMO2 promoter and transactivates LMO2 expression; c-myb silencing in CD34+ cells impairs erythroid differentiation, and LMO2 overexpression partially rescues the erythroid defect, placing c-myb upstream of LMO2 in erythropoiesis. Chromatin immunoprecipitation, luciferase reporter assay, retroviral overexpression, c-myb siRNA knockdown Blood High 20686118
2010 In DLBCL, the LMO2 complex contains LDB1, E2A, HEB, Lyl1, ETO2, and SP1 but not TAL1 or GATA proteins; novel partners ELK1, NFATc1, and LEF1 were identified; LMO2 increases NFATc1 transcriptional activity and decreases LEF1 activity. Co-immunoprecipitation/MS interactome, reporter assays Blood Medium 22517897
2011 The GATA1 N-terminal finger can simultaneously bind both LMO2 and FOG1; LMO2 in turn simultaneously contacts GATA1 and TAL1/E2A at bipartite E-box/WGATAR sites, providing structural evidence for cooccupancy of FOG1 and TAL1/E2A/LMO2/LDB1 at GATA1-dependent genes. NMR structure, EMSA, pulldown assays Proceedings of the National Academy of Sciences of the United States of America High 21844373
2012 KDM3B, a JmjC domain-containing histone H3K9-me1/2 demethylase, activates lmo2 expression through synergistic interaction with the histone acetyltransferase CBP; KDM3B occupies the lmo2 locus and its knockdown reduces LMO2 levels. ChIP-chip genome-wide, in vitro demethylase assay, co-immunoprecipitation with CBP Molecular and cellular biology High 22615488
2013 Crystal structure of the (SCL:E47)bHLH:LMO2:LDB1LID complex bound to DNA revealed that LMO2 induces new hydrogen bonds in SCL:E47 upon binding, strengthening heterodimer formation and imposing a rotation on E47 that weakens heterodimer:DNA interaction, shifting DNA-binding to additional partners. X-ray crystallography of multiprotein-DNA complex, biochemical binding analyses Cell reports High 23831025
2013 Lmo2 must recruit Lyl1 (but not Scl/Tal1) to DNA to drive T-cell leukemia; Lyl1 deletion abolishes all oncogenic functions of Lmo2 including upregulation of stem cell-like gene signature, aberrant thymocyte self-renewal, and T-cell leukemia development. Conditional knockout of Scl or Lyl1 in Lmo2-transgenic mice, transplantation assay, gene expression profiling Blood High 23926305
2013 GATA2 and Lmo2 directly regulate neuropilin-2 (NRP2) expression in endothelial cells; silencing either factor reduces NRP2 at protein, mRNA and promoter levels, and NRP2 overexpression partially rescues impaired angiogenic sprouting caused by GATA2/Lmo2 knockdown. siRNA knockdown, promoter reporter assay, NRP2 rescue overexpression, embryoid body angiogenesis assay Angiogenesis High 23892628
2014 HHEX is a direct transcriptional target of LMO2; LMO2 occupies the HHEX promoter, and 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, conditional knockout of Hhex in Lmo2-transgenic mice, T-ALL development monitoring PloS one High 24465765
2014 A conformational difference in the LMO2 LIM domain positioning (bending at a central helical region) was revealed by crystal structure of LMO2 with an inhibitory single-domain antibody, supporting a model in which newly synthesized LMO2 is intrinsically disordered and binds a partner protein to nucleate further complex assembly. X-ray crystallography of LMO2:VH single-domain antibody complex Scientific reports High 24407558
2016 LMO2 is recruited to DNA replication origins through interaction with POLD1 (DNA polymerase delta), PRIM1 (DNA primase), and MCM6; tethering LMO2 to synthetic DNA sequences converts them into replication origins; lowering LMO2 in erythroid progenitors delays G1-S progression, while ectopic expression in thymocytes drives DNA replication and cell cycle entry. Co-immunoprecipitation with replication enzymes, synthetic origin tethering assay, BrdU incorporation, ChIP at replication origins Proceedings of the National Academy of Sciences of the United States of America High 26764384
2017 In basal-type breast cancer cells, LMO2 localizes predominantly to the cytoplasm where it interacts with cofilin1 to regulate actin cytoskeleton dynamics, promoting tumor cell migration and invasion. Subcellular fractionation, co-immunoprecipitation with cofilin1, migration/invasion assays, SCID mouse metastasis model Oncotarget Medium 27880729
2017 Lmo2 directly regulates Sphk1 gene expression in endothelial cells by binding to the Sphk1 promoter (shown by ChIP-PCR); Lmo2 knockdown reduces Sphk1 expression and impairs endothelial cell migration and intersegmental vessel formation; Sphk1 mRNA rescues the Lmo2 KD phenotype. ChIP-PCR, morpholino knockdown in zebrafish, scratch assay, aortic ring assay, mRNA rescue Arteriosclerosis, thrombosis, and vascular biology High 28775072
2017 Recurrent intronic mutations in LMO2 in T-ALL create de novo MYB, ETS1, or RUNX1 binding sites that activate a neomorphic promoter, causing monoallelic LMO2 overexpression; CRISPR/Cas9 disruption of the mutant allele markedly downregulates LMO2 expression. 5'-capped RNA transcript mapping, CRISPR/Cas9 allele-specific disruption, transcription factor binding site analysis Blood High 28270453
2017 LMO2 is required for TAL1 DNA-binding activity at hematopoietic regulatory elements; in Lmo2-/- cells, target site recognition of TAL1 is impaired genome-wide, and LMO2 positions the TAL1/LMO2/LDB1 complex at regulatory elements important for the haematopoietic developmental program. Lmo2-/- ES cell differentiation, genome-wide ChIP-seq for TAL1 and LMO2, comparison with Tal1-/- cells Nucleic acids research High 28973433
2019 LMO2 inhibits BRCA1 recruitment to DNA double-strand breaks by interacting with 53BP1 during repair, rendering LMO2-positive DLBCL and T-ALL cells deficient in homologous recombination and sensitive to PARP inhibitors. Co-immunoprecipitation of LMO2 with 53BP1, BRCA1 recruitment assay at DSB sites, HR functional assay, PARP inhibitor sensitivity Cancer cell High 31447348
2019 LMO2 is deacetylated on lysine 74 and 78 by the NAMPT/SIRT2 pathway; deacetylation enables LMO2 to interact with LDB1 and activate the TAL1 complex; NAMPT or SIRT2 inhibition suppresses T-ALL cell growth by diminishing LMO2 deacetylation. Mass spectrometry of LMO2 acetylation sites, SIRT2 deacetylase assay, Co-IP of deacetylated LMO2 with LDB1, NAMPT/SIRT2 inhibitor treatment, zebrafish blood formation assay Blood High 31366618
2021 Lmo2 directly binds the prdm16 promoter in endothelial cells (shown by ChIP-PCR) and regulates prdm16 transcription; lmo2 loss-of-function in zebrafish reduces prdm16 expression and impairs angiogenesis, establishing an Lmo2-Prdm16 axis in angiogenesis. ChIP-PCR, lmo2 loss-of-function zebrafish, RNA-seq comparison of endothelial cell populations Proceedings of the National Academy of Sciences of the United States of America Medium 34330825
2005 Human Bex2 specifically interacts with LMO2 (shown by GST pull-down and co-immunoprecipitation) and forms part of a DNA-binding complex with LMO2, enhancing LMO2 transcriptional activity; LMO2 also interacts with neuronal bHLH protein NSCL2 and upregulates NSCL2-dependent transcription. GST pull-down, co-immunoprecipitation, EMSA, mammalian two-hybrid, reporter assay Nucleic acids research Medium 16314316
1995 The N-terminal portions of RBTN1 and RBTN2 (LMO2) support transcriptional transactivation in transfection assays; the NH2-terminal 27 amino acids of RBTN2 are sufficient for transactivation in yeast, and RBTN2 forms homodimers. Transfection reporter assays, yeast two-hybrid and transactivation assay Oncogene Medium 7731680
2012 LMO2 directly assembles TAL1-E47/LYL1 dimers with GATA2 at the ANG-2 promoter in endothelial cells; ChIP demonstrated occupancy of TAL1, LYL1, LMO2, and GATA2 at an E-box/GATA composite element; knockdown of any factor reduces ANG-2 expression. ChIP, siRNA knockdown, promoter reporter assay, co-immunoprecipitation PloS one High 22792348

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.) 2778 14564000
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 257 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
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
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 134 17038524
2006 The cryptic chromosomal deletion del(11)(p12p13) as a new activation mechanism of LMO2 in pediatric T-cell acute lymphoblastic leukemia. Blood 130 16873670
2016 TTG2 controls the developmental regulation of seed coat tannins in Arabidopsis by regulating vacuolar transport steps in the proanthocyanidin pathway. Developmental biology 122 27046632
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
1992 T-cell acute lymphoblastic lymphoma induced in transgenic mice by the RBTN1 and RBTN2 LIM-domain genes. Oncogene 112 1461647
2008 The maternally expressed WRKY transcription factor TTG2 controls lethality in interploidy crosses of Arabidopsis. PLoS biology 106 19071961
2017 A Grapevine TTG2-Like WRKY Transcription Factor Is Involved in Regulating Vacuolar Transport and Flavonoid Biosynthesis. Frontiers in plant science 96 28105033
2012 KDM3B is the H3K9 demethylase involved in transcriptional activation of lmo2 in leukemia. Molecular and cellular biology 94 22615488
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 94 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 92 20686118
2010 A self-inactivating lentiviral vector for SCID-X1 gene therapy that does not activate LMO2 expression in human T cells. Blood 90 20457870
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
2011 Notch1 inhibition targets the leukemia-initiating cells in a Tal1/Lmo2 mouse model of T-ALL. Blood 84 21670468
2005 Regulation of the lmo2 promoter during hematopoietic and vascular development in zebrafish. Developmental biology 82 15893977
1995 The oncogenic LIM protein Rbtn2 causes thymic developmental aberrations that precede malignancy in transgenic mice. Oncogene 78 7545805
2001 Primitive erythropoiesis in the Xenopus embryo: the synergistic role of LMO-2, SCL and GATA-binding proteins. Development (Cambridge, England) 73 11493549
2017 Activation of the LMO2 oncogene through a somatically acquired neomorphic promoter in T-cell acute lymphoblastic leukemia. Blood 67 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
2019 LMO2 Confers Synthetic Lethality to PARP Inhibition in DLBCL. Cancer cell 63 31447348
2014 Arabidopsis TTG2 regulates TRY expression through enhancement of activator complex-triggered activation. The Plant cell 63 25304203
2009 Murine leukemias with retroviral insertions at Lmo2 are predictive of the leukemias induced in SCID-X1 patients following retroviral gene therapy. PLoS genetics 62 19461887
2003 Structural basis for the recognition of ldb1 by the N-terminal LIM domains of LMO2 and LMO4. The EMBO journal 61 12727888
2010 Structure of the leukemia oncogene LMO2: implications for the assembly of a hematopoietic transcription factor complex. Blood 60 21076045
2015 LMO2 at 25 years: a paradigm of chromosomal translocation proteins. Open biology 59 26108219
2013 Requirement for Lyl1 in a model of Lmo2-driven early T-cell precursor ALL. Blood 58 23926305
2013 Structural basis for LMO2-driven recruitment of the SCL:E47bHLH heterodimer to hematopoietic-specific transcriptional targets. Cell reports 57 23831025
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2013 TTG2-regulated development is related to expression of putative AUXIN RESPONSE FACTOR genes in tobacco. BMC genomics 18 24252253
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