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

Jögi, Annika LU ; Persson, Paula LU ; Grynfeld, Anna LU ; Påhlman, Sven LU and Axelson, Håkan LU (2002) In Journal of Biological Chemistry 277(11). p.9118-9126
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
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
in
Journal of Biological Chemistry
volume
277
issue
11
pages
9118 - 9126
publisher
ASBMB
external identifiers
  • pmid:11756408
  • wos:000174400600052
  • scopus:0037088678
ISSN
1083-351X
DOI
10.1074/jbc.M107713200
language
English
LU publication?
yes
id
ef8157d6-7191-427a-a1f5-0ef2b7655969 (old id 106917)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11756408&dopt=Abstract
date added to LUP
2007-07-25 14:11:13
date last changed
2017-11-12 03:25:07
@article{ef8157d6-7191-427a-a1f5-0ef2b7655969,
  abstract     = {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.},
  author       = {Jögi, Annika and Persson, Paula and Grynfeld, Anna and Påhlman, Sven and Axelson, Håkan},
  issn         = {1083-351X},
  keyword      = {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},
  language     = {eng},
  number       = {11},
  pages        = {9118--9126},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Modulation of Basic Helix-Loop-Helix Transcription Complex Formation by Id Proteins during Neuronal Differentiation.},
  url          = {http://dx.doi.org/10.1074/jbc.M107713200},
  volume       = {277},
  year         = {2002},
}