Document Detail

Neuronal PAS domain protein 1 is a transcriptional repressor and requires arylhydrocarbon nuclear translocator for its nuclear localization.
MedLine Citation:
PMID:  16954219     Owner:  NLM     Status:  MEDLINE    
Neuronal PAS domain protein 1 (NPAS1), a basic helix-loop-helix-PAS transcription factor expressed in the central nervous system, has been suggested to be involved in neuronal differentiation. However, relatively little is known about the molecular mechanism underlying the role of NPAS1 during development. In this study we set out to characterize the different domains within NPAS1. We showed that the nuclear localization of NPAS1 is dependent on the presence of ARNT. In addition, the transcriptional potential of ARNT is not required for this localization. In the absence of ARNT, NPAS1 is excluded from the nucleus, and this exclusion is due to the presence of a nuclear export signal within the N terminus of NPAS1. The interaction between NPAS1 and ARNT is via their N termini. We found no transactivation domain within NPAS1; instead, we mapped out at least three repression domains within NPAS1, suggesting that NPAS1 acts as a repressor. Furthermore, our experiments showed that NPAS1 is able to repress the transactivation functions of ARNT and ARNT2. We suggest that NPAS1 is guided into the nucleus by ARNT via the ARNT nuclear localization signal, and NPAS1 can override the activation function of adjacent transcription factors, providing a mechanism by which NPAS1 may inhibit transcription.
Christina H L Teh; Kevin K Y Lam; Chin C Loh; Jia M Loo; Tie Yan; Tit Meng Lim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-09-05
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  281     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-11-06     Completed Date:  2006-12-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  34617-29     Citation Subset:  IM    
Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Kent Ridge, Singapore 117542.
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MeSH Terms
Aryl Hydrocarbon Receptor Nuclear Translocator / genetics,  metabolism*
Basic Helix-Loop-Helix Transcription Factors / genetics,  metabolism*
Binding Sites
Blotting, Western
Cell Nucleus / metabolism*
Cells, Cultured
Cloning, Molecular
Immunoenzyme Techniques
Kidney / cytology,  metabolism
Mice, Inbred C57BL
Nerve Tissue Proteins / genetics,  metabolism*
Neurons / cytology,  metabolism
Plasmids / genetics
Protein Binding
Protein Transport
Receptors, Aryl Hydrocarbon
Repressor Proteins / genetics,  metabolism*
Saccharomyces cerevisiae
Transcription, Genetic*
Transcriptional Activation
Two-Hybrid System Techniques
Reg. No./Substance:
0/Arnt protein, mouse; 0/Arnt2 protein, mouse; 0/Basic Helix-Loop-Helix Transcription Factors; 0/Nerve Tissue Proteins; 0/Npas1 protein, mouse; 0/Receptors, Aryl Hydrocarbon; 0/Repressor Proteins; 138391-32-9/Aryl Hydrocarbon Receptor Nuclear Translocator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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