Håkan Axelson
Research team manager
Modulation of Basic Helix-Loop-Helix Transcription Complex Formation by Id Proteins during Neuronal Differentiation.
Author
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
Links
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