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Trichostatin A (TSA, a HDAC inhibitor) addition significantly attenuates MTX unsensitivity caused by dysfunction of LMO2/ZEB1 signaling. In conclusion, these findings have identified a molecular mechanism underlying LMO2/ZEB1-mediated leukaemogenesis, paving a way for treating T-ALL with a new strategy of epigenetic inhibitors.
Genome-wide analysis indicated that LMO2 is required at the hemangioblast stage to position the TAL1 (显示 TAL1 蛋白)/LMO2/LDB1 (显示 LDB1 蛋白) complex to regulatory elements that are important for the establishment of the hematopoietic developmental program.
DNM2 (显示 DNM2 蛋白) mutations cooperate with Lmo2 T-cell oncogenes by enhancing IL-7 (显示 IL7 蛋白) signalling.
Hhex (显示 HHEX 蛋白) regulates Kit to promote radioresistance of self-renewing thymocytes in Lmo2-transgenic mice.
HHEX (显示 HHEX 蛋白) is a direct transcriptional target of LMO2 consistent with its concordant gene expression.
GATA2 (显示 GATA2 蛋白) and Lmo2 cooperatively regulate VEGF (显示 VEGFA 蛋白)-induced angiogenesis and lymphangiogenesis via NRP2 (显示 NRP2 蛋白).
a regulatory hierarchy of HOX control of LMO2 in normal development
Lyl1 is critical for all oncogenic functions of Lmo2, including upregulation of a stem cell-like gene signature, aberrant self-renewal of thymocytes, and subsequent generation of T-cell leukemia.
A model in which the distal control region functions through a chromatin looping mechanism to contact and enhance Lmo2 transcription specifically in erythroid cells.
Studied the solution structure of Lmo2(LIM2 (显示 LHX2 蛋白)) /Ldb1 (显示 LDB1 蛋白)(LID) complex. Results show modular binding of tandem LIM (显示 PDLIM5 蛋白) domains in Lmo2 to tandem linear motifs in Ldb1 (显示 LDB1 蛋白) is accompanied by several disorder-to-order transitions/ conformational changes in both proteins.
the data in this study revealed a novel crosstalk between LMO2 and the Wnt (显示 WNT2 蛋白) signaling pathway during tumorigenesis and suggested that LMO2 might be a tumor suppressor in certain solid tumors.
LMO2 has a predominantly cytoplasmic location in breast cancer cells. LMO2 interaction with cofilin1 regulates actin cytoskeleton dynamics, promoting tumor cell invasion and metastasis.
These data indicate that Lhx2 (显示 LHX2 蛋白) is capable of blocking proliferation of T-ALL-derived cells by both LMO2-dependent and -independent means. We propose Lhx2 (显示 LHX2 蛋白) as a new molecular tool for anti-T-ALL drug development.
stromal LMO2 may be responsible for zonal characteristic of Prostate cancer
The transcriptional factor LMO2 regulates endothelial proliferation and angiogenesis in vitro.
This article demonstrates a novel and unexpected function of the LMO2 oncogenic transcription factor in controlling DNA replication that we unravelled via an unbiased proteome-wide screen for LMO2-interacting partners.
Findings suggest that LMO2 loss may be a good predictor for the presence of MYC (显示 MYC 蛋白) translocation in large B-cell lymphoma.
FOXP3 (显示 FOXP3 蛋白) binds LMO2 in vitro, resulting in decreased interaction between LMO2 and TAL1 (显示 TAL1 蛋白), providing a molecular mechanism for FOXP3 (显示 FOXP3 蛋白)-mediated transcriptional modulation in T-ALL.
recurrent activating intronic mutations of LMO2, a prominent oncogene (显示 RAB1A 蛋白) in T-cell acute lymphoblastic leukemia (T-ALL). Heterozygous mutations were identified in PF-382 and DU.528 T-ALL cell lines in addition to 3.7% of pediatric (6 of 160) and 5.5% of adult (9 of 163) T-ALL patient samples.
Data indicate a novel functional mechanism of LMO2 in facilitating the delivery of actin monomers to the branched microfilament and increasing lamellipodia/filopodia formation in basal-type breast cancer cells.
The transcriptional factor LMO2 regulates endothelial proliferation and angiogenesis in vitro. Furthermore, LMO2 is required for angiogenesis and tissue healing in vivo. Thus, LMO2 is a critical determinant of vascular and tissue regeneration.
a loss-of-function mutation in lmo2, a gene specifically required for hematopoiesis and vascular development, results in failure of optic fissure closure
in the absence of inducers of erythroid or myeloid haematopoiesis, Scl/Tal1 (显示 TAL1 蛋白)-Lmo2-induced haemangioblasts differentiate into endothelial cells
Transcriptional regulation of lmo2 promoter during hematopoietic and vascular development in zebrafish is elucidated.
Scl (显示 TAL1 蛋白)/Lmo2 complex does not appear to autoregulate, as neither gene's expression is affected by depletion of the other
LMO2 encodes a cysteine-rich, two LIM-domain protein that is required for yolk sac erythropoiesis. The LMO2 protein has a central and crucial role in hematopoietic development and is highly conserved. The LMO2 transcription start site is located approximately 25 kb downstream from the 11p13 T-cell translocation cluster (11p13 ttc), where a number T-cell acute lymphoblastic leukemia-specific translocations occur. Alternative splicing results in multiple transcript variants encoding different isoforms.
, LIM domain only 2 (rhombotin-like 1)
, LIM domain only protein 2
, LIM only 2
, T-cell translocation protein 2
, cysteine-rich protein TTG-2
, T-cell translocation gene 2
, rhombotin 2
, rhombotin-like 1
, LIM domain only-2