Document Detail

The Nk-2 box of the Drosophila homeodomain protein, Vnd, contributes to its repression activity in a Groucho-dependent manner.
MedLine Citation:
PMID:  17070676     Owner:  NLM     Status:  MEDLINE    
The transcription factor, Vnd, is a dual regulator that specifies ventral neuroblast identity in Drosophila by both repressing and activating target genes. Vnd and its homologues have a conserved amino acid sequence, the Nk-2 box or Nk specific domain, as well a conserved DNA-binding homeodomain and an EhI-type Groucho interaction domain. However, the function of the conserved Nk-2 box has not been fully defined. To explore its function, we deleted the Nk-2 box and compared the regulatory activity of mutant Vnd in transgenic over-expression assays to that of the wild-type protein. We were unable to assign regulatory activity to the Nk-2 box using an over-expression assay, because the mutant protein activated expression of endogenous Vnd, masking a requirement for the Nk-2 box. However, in transgenic rescue assays, Vnd lacking the Nk-2 box repressed ind expression at 30% lower levels than the wild-type protein. Moreover, in transient transfection assays using Gal4 DNA-binding domain-Vnd chimeras, the repression activity of Vnd lacking the Nk-2 box was compromised. Because Vnd represses target gene expression in conjunction with Groucho, we asked whether the Nk-2 box affects Vnd's ability to interact with this co-repressor. Vnd lacking the Nk-2 box binds Groucho 30% less efficiently than wild-type Vnd in co-immunoprecipitations. These data suggest that the Nk-2 box contributes to the repression activity of Vnd by stabilizing its interaction with the co-repressor, Groucho.
Jay Uhler; Huanqing Zhang; Li-Jyun Syu; Dervla M Mellerick
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-08-02
Journal Detail:
Title:  Mechanisms of development     Volume:  124     ISSN:  0925-4773     ISO Abbreviation:  Mech. Dev.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-12     Completed Date:  2007-02-27     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  9101218     Medline TA:  Mech Dev     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  1-10     Citation Subset:  IM    
Pathology Department, University of Michigan, Ann Arbor, MI 48109-0646, USA.
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MeSH Terms
Amino Acid Sequence
Animals, Genetically Modified
Base Sequence
Basic Helix-Loop-Helix Transcription Factors / genetics,  metabolism*
Conserved Sequence
DNA, Complementary / genetics
Drosophila Proteins / chemistry*,  genetics,  metabolism*
Drosophila melanogaster / embryology,  genetics,  metabolism*
Gene Expression Regulation, Developmental
Genes, Homeobox
Genes, Insect
Homeodomain Proteins / chemistry*,  genetics,  metabolism*
Molecular Sequence Data
Nervous System / embryology,  metabolism
Protein Binding
Protein Structure, Tertiary
Repressor Proteins / chemistry,  genetics,  metabolism*
Sequence Deletion
Transcription Factors / chemistry*,  genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/DNA, Complementary; 0/Drosophila Proteins; 0/Homeodomain Proteins; 0/Repressor Proteins; 0/Transcription Factors; 0/groucho protein, Drosophila; 0/vnd protein, Drosophila

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

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