Isolation and chromosomal assignment of human genes encoding cofactor of LIM homeodomain proteins, CLIM1 and CLIM2

Ueki, Nobuhide; Seki, Naohiko; Yano, Kazuhiro; Ohira, Miki; Masuho, Yasuhiko; Muramatsu, Masaaki

doi:10.1007/s100380050120

Cited by 7 publications

(6 citation statements)

References 20 publications

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“…The LIM domain binding 2 (LDB2), involved in the maintenance of cell homeostasis (51), and SEPW1, a gene with antioxidant function (52) that could play a role in protection from oxidative stress, are respectively down-and up-regulated in multiple myeloma endothelial cells. SEPW1-mediated homeostasis seems to be crucial for angiogenesis in multiple myeloma because small interfering RNA-silenced expression of the gene inhibited multiple myeloma endothelial cell adhesion and angiogenic activity.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling of Bone Marrow Endothelial Cells in Patients with Multiple Myeloma

Ria

Todoerti

Berardi

et al. 2009

Clinical Cancer Research

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Purpose: To determine a "gene/molecular fingerprint" of multiple myeloma endothelial cells and identify vascular mechanisms governing the malignant progression from quiescent monoclonal gammopathy of undetermined significance. Experimental Design: Comparative gene expression profiling of multiple myeloma endothelial cells and monoclonal gammopathy of undetermined significance endothelial cells with the Affymetrix U133A Arrays was carried out in patients at diagnosis; expression and function of selective vascular markers was validated by real-time reverse transcriptase-PCR, Western blot, and small interfering RNA analyses. Results: Twenty-two genes were found differentially expressed (14 down-regulated and eight up-regulated) at relatively high stringency in multiple myeloma endothelial cells compared with monoclonal gammopathy of undetermined significance endothelial cells. Functional annotation revealed a role of these genes in the regulation of extracellular matrix formation and bone remodeling, cell adhesion, chemotaxis, angiogenesis, resistance to apoptosis, and cell-cycle regulation. Validation was focused on six genes (DIRAS3, SERPINF1, SRPX, BNIP3, IER3, and SEPW1) not previously found to be functionally correlated to the overangiogenic phenotype of multiple myeloma endothelial cells in active disease. The small interfering RNA knockdown of BNIP3, IER3, and SEPW1 genes affected critical multiple myeloma endothelial cell functions correlated with the overangiogenic phenotype. Conclusions: The distinct endothelial cell gene expression profiles and vascular phenotypes detected in this study may influence remodeling of the bone marrow microenvironment in patients with active multiple myeloma. A better understanding of the linkage between plasma cells and endothelial cells in multiple myeloma could contribute to the molecular classification of the disease and thus pinpoint selective gene targets for more effective antiangiogenic treatments. (Clin Cancer Res 2009;15(17):5369-78) The unique markers expressed by tumor vasculature distinguish it from normal endothelium. These abnormalities reflect the pathologic nature of its induction and attempts to discover tumor endothelial cell markers have always been hampered by technical difficulties in isolating functionally intact and phenotypically stable endothelial cells from patient samples. St. Croix et al. (1) were the first to show that colorectal cancer endothelial cells overexpress specific transcripts as a result of qualitative

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Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling of Bone Marrow Endothelial Cells in Patients with Multiple Myeloma

Ria

Todoerti

Berardi

et al. 2009

Clinical Cancer Research

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“…LDB2 is one of the members of the LIM binding protein family. Members of this family are essential regulators of LIM homeodomain proteins by working as adapter molecules allowing assembly of transcriptional regulatory complexes . It has been reported that LDB2 expressed abundantly in the vasculature during zebrafish embryogenesis and might be involved in cardiovascular diseases .…”

Section: The Primer Sequences Primer Locations and Product Size Of Qpcrmentioning

confidence: 99%

“…Members of this family are essential regulators of LIM homeodomain proteins by working as adapter molecules allowing assembly of transcriptional regulatory complexes. 8 It has been reported that LDB2 expressed abundantly in the vasculature during zebrafish embryogenesis and might be involved in cardiovascular diseases. 9 NR_130734 localizes between 16 752 473 and 16 900 432 bp on chromosome 4, containing seven exons and six introns with a length of 944 bp.…”

Section: Wolf-hirschhorn Syndrome (Whs; Online Mendelianmentioning

confidence: 99%

A genotype–phenotype correlation study reveals that a non‐coding RNA might be associated with cardiovascular anomalies in fetuses with WHS

Tao

Wang

et al. 2016

Prenatal Diagnosis

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What's Already Known About This Topic? Wolf–Hirschhorn syndrome is a genetic disorder caused by partial deletion of the short arm of chromosome It consists of a broad spectrum of clinical manifestations. The deletion size also varies significantly. What Does This Study Add? This study found that a non‐coding RNA (NR_130734) might be involved in cardiovascular development by analyzing the genotype–phenotype correlation of two fetuses with Wolf–Hirschhorn syndrome.

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“…One of which is a human 36 kDa protein (CLIM1), containing a N-terminal PDZ domain and a C-terminal LIM domain. This Enigma protein has been renamed El®n to avoid confusion of this protein with LIMdomain binding protein LDB2, also known as CLIM1 [Ueki et al, 1999]. El®n is a protein most abundantly expressed in heart .…”

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confidence: 99%

Elfin is expressed during early heart development*

Kotaka

Lau

Cheung

et al. 2001

J of Cellular Biochemistry

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Elfin (previously named CLIM1) is a protein that possesses an N-terminal PDZ domain and a C-terminal LIM domain. It belongs to the family of Enigma proteins. Enigma proteins are a family of cytoplasmic proteins that contain an N-terminal PDZ domain and a series of C-terminal LIM domains. By virtue of these two protein interacting domains, Enigma proteins are capable of protein-protein interactions. It has been proposed that Enigma proteins may act as adapters between kinases and the cytoskeleton. We have previously shown that Elfin is most abundantly expressed in the heart and it colocalizes with alpha-actinin 2 at the Z-disks of the myocardium. In this report, Elfin was shown to localize at the actin stress fibers of myoblasts, as revealed by green fluorescent protein (GFP) tagging. In situ hybridization and immunostaining showed that Elfin expression begins at an early stage in mouse development and is present throughout the developing heart. Taken together, our experimental results suggest that Elfin may play an important role in myofibrillogenesis and heart development.

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Isolation and chromosomal assignment of human genes encoding cofactor of LIM homeodomain proteins, CLIM1 and CLIM2

Cited by 7 publications

References 20 publications

Gene Expression Profiling of Bone Marrow Endothelial Cells in Patients with Multiple Myeloma

Gene Expression Profiling of Bone Marrow Endothelial Cells in Patients with Multiple Myeloma

A genotype–phenotype correlation study reveals that a non‐coding RNA might be associated with cardiovascular anomalies in fetuses with WHS

Elfin is expressed during early heart development*

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