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Håkan Axelson

Håkan Axelson

Research team manager

Håkan Axelson

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

Summary, in 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.

Department/s

  • Department of Translational Medicine
  • Division of Molecular Medicine and Gene Therapy

Publishing year

2002

Language

English

Pages

9118-9126

Publication/Series

Journal of Biological Chemistry

Volume

277

Issue

11

Document type

Journal article

Publisher

American Society for Biochemistry and Molecular Biology

Topic

  • Cancer and Oncology

Keywords

  • 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

Status

Published

ISBN/ISSN/Other

  • ISSN: 1083-351X