Human Bex2 interacts with LMO2 and regulates the transcriptional activity of a novel DNA-binding complex

Human Bex2 (brain expressed X-linked, hBex2) is highly expressed in the embryonic brain, but its function remains unknown. We have identified that LMO2, a LIM-domain containing transcriptional factor, specifically interacts with hBex2 but not with mouse Bex1 and Bex2. The interaction was confirmed both by pull-down with GST-hBex2 and by coimmunoprecipitation assays in vivo. Using electrophoretic mobility shift assay, we have demonstrated the physical interaction of hBex2 and LMO2 as part of a DNA-binding protein complex. We have also shown that hBex2 can enhance the transcriptional activity of LMO2 in vivo. Furthermore, using mammalian two-hybrid analysis, we have identified a neuronal bHLH protein, NSCL2, as a novel binding partner for LMO2. We then showed that LMO2 could up-regulate NSCL2-dependent transcriptional activity, and hBex2 augmented this effect. Thus, hBex2 may act as a specific regulator during embryonic development by modulating the transcriptional activity of a novel E-box sequence-binding complex that contains hBex2, LMO2, NSCL2 and LDB1.

• Publication year

  2005

• Venue

  Nucleic Acids Research

• Publication date

  2005-11-24

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1093/nar/gki964PMID 16314316PMCID 1298925
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Characterization of the Bex gene family in humans, mice, and rats.

  2005influential reference
• Immunolocalization of Bex protein in the mouse brain and olfactory system

  2005cited by this paper
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  2003cited by this paper
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  2003cited by this paper
• Transcription regulator LMO4 interferes with neuritogenesis in human SH-SY5Y neuroblastoma cells.

  2003cited by this paper
• The LIM-only protein LMO4 modulates the transcriptional activity of HEN1.

  2003influential reference
• Nerve growth factor-dependent regulation of NADE-induced apoptosis.

  2003influential reference
• Identification of members of the Bex gene family as olfactory marker protein (OMP) binding partners

  2003cited by this paper
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  2002cited by this paper
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  2002cited by this paper
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  2002cited by this paper
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  2001cited by this paper
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  2000influential reference
• A Pentamer Transcriptional Complex Including tal-1 and Retinoblastoma Protein Downmodulates c-kit Expression in Normal Erythroblasts

  2000cited by this paper
• Regulation of neurogenesis by interactions between HEN1 and neuronal LMO proteins.

  2000cited by this paper
• Expression of LMO-4 in the central nervous system of the embryonic and adult mouse.

  1999cited by this paper
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  1999cited by this paper
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  1998cited by this paper
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  1997cited by this paper
• [Differential display analysis of human fetal brain mRNAs and isolation of brain-specific novel ESTs].

  1997cited by this paper
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  1995cited by this paper
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  1994cited by this paper
• HEN1 and HEN2: a subgroup of basic helix-loop-helix genes that are coexpressed in a human neuroblastoma.

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  1992cited by this paper
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  1992cited by this paper
• NSCL-2: a basic domain helix-loop-helix gene expressed in early neurogenesis.

  1992cited by this paper
• Molecular characterization of NSCL, a gene encoding a helix-loop-helix protein expressed in the developing nervous system.

  1992cited by this paper
• Developmentally regulated and tissue specific expression of mRNAs encoding the two alternative forms of the LIM domain oncogene rhombotin: evidence for thymus expression.

  1991cited by this paper
• The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13.

  1991cited by this paper
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  1990cited by this paper
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  1989cited by this paper

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