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Modulation of Basic Helix-Loop-Helix Transcription Complex Formation by Id Proteins during Neuronal Differentiation.

Author:
  • Annika Jögi
  • Paula Persson
  • Anna Grynfeld
  • Sven Påhlman
  • Håkan Axelson
Publishing year: 2002
Language: English
Pages: 9118-9126
Publication/Series: Journal of Biological Chemistry
Volume: 277
Issue: 11
Document type: Journal article
Publisher: ASBMB

Abstract english

It is assumed that the Id helix-loop-helix (HLH) proteins act by associating with ubiquitously expressed basic HLH (bHLH) transcription factors, such as E47 and E2-2, which prevents these factors from forming functional hetero- or homodimeric DNA binding complexes. Several tissue-specific bHLH proteins, including HASH-1, dHAND, and HES-1, are important for development of the nervous system. Neuroblastoma tumors are derived from the sympathetic nervous system and exhibit neural crest features. In differentiating neuroblastoma cells, HASH-1 is down-regulated, and there is coincident up-regulation of the transcriptional repressor HES-1, which is known to bind the HASH-1 promoter. We found that the three Id proteins expressed in neuroblastoma cells (Id1, Id2, and Id3) were down-regulated during induced differentiation, indicating that Id proteins help keep the tumor cells in an undifferentiated state. Studying interactions, we noted that all four Id proteins could dimerize with E47 or E2-2, but not with HASH-1 or dHAND. However, the Id proteins did complex with HES-1, and increased levels of Id2 reduced the DNA binding activity of HES-1. Furthermore, HES-1 interfered with Id2/E2-2 complex formation. The ability of Id proteins to affect HES-1 activity is of particular interest in neuronal cells, where regulation of HES-1 is essential for the timing of neuronal differentiation.

Keywords

  • Cancer and Oncology
  • Transcription Factors : genetics : metabolism
  • Support Non-U.S. Gov't
  • Promoter Regions (Genetics)
  • Neurons : physiology
  • Homeodomain Proteins : metabolism
  • Cell Differentiation
  • DNA-Binding Proteins : genetics : metabolism
  • Tumor Cells Cultured
  • Two-Hybrid System Techniques

Other

Published
  • ISSN: 1083-351X
Håkan Axelson
E-mail: hakan [dot] axelson [at] med [dot] lu [dot] se

Professor

Division of Translational Cancer Research

+46 46 222 64 34

MV 404 A31A2

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