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The transcriptional repressor dMnt is a regulator of growth in Drosophila melanogaster.

Loo, Lenora W M and Secombe, Julie and Little, John T and Carlos, Leni-Sue and Yost, Cynthia and Cheng, Pei-Feng and Flynn, Erin M and Edgar, Bruce A and Eisenman, Robert N (2005) The transcriptional repressor dMnt is a regulator of growth in Drosophila melanogaster. Molecular and cellular biology, 25 (16). pp. 7078-7091. ISSN 0270-7306

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The Myc-Max-Mad/Mnt network of transcription factors has been implicated in oncogenesis and the regulation of proliferation in vertebrate cells. The identification of Myc and Max homologs in Drosophila melanogaster has demonstrated a critical role for dMyc in cell growth control. In this report, we identify and characterize the third member of this network, dMnt, the sole fly homolog of the mammalian Mnt and Mad family of transcriptional repressors. dMnt possesses two regions characteristic of Mad and Mnt proteins: a basic helix-loop-helix-zipper domain, through which it dimerizes with dMax to form a sequence-specific DNA binding complex, and a Sin-interacting domain, which mediates interaction with the dSin3 corepressor. Using the upstream activation sequence/GAL4 system, we show that expression of dMnt results in an inhibition of cellular growth and proliferation. Furthermore, we have generated a dMnt null allele, which results in flies with larger cells, increased weight, and decreased life span compared to wild-type flies. Our results demonstrate that dMnt is a transcriptional repressor that regulates D. melanogaster body size.

Item Type: Article or Abstract
Additional Information: This article is freely available in PubMed Central and at the journal's website via the Article URL above.
DOI: 10.1128/MCB.25.16.7078-7091.2005
PubMed ID: 16055719
PMCID: PMC1190258
Grant Numbers: RO1 CA15738, R01 GM51186, F32 GM18246-02
Keywords or MeSH Headings: Alleles; Alternative Splicing; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Body Size; Cell Proliferation; Cell Separation; DNA/metabolism; DNA-Binding Proteins/genetics/metabolism; Dimerization; Drosophila Proteins/genetics/metabolism; Drosophila melanogaster/growth & development/physiology; Flow Cytometry; Glutathione Transferase/metabolism; Green Fluorescent Proteins/metabolism; Immunohistochemistry; Insulin/metabolism; Longevity; Models, Genetic; Mutation; Phenotype; Phylogeny; Protein Binding; Protein Structure, Tertiary; Recombinant Fusion Proteins/metabolism; Repressor Proteins/metabolism/physiology; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Transcription Factors/genetics/metabolism; Transcription, Genetic; Two-Hybrid System Techniques;
Subjects: Molecules > Proteins > Transcription factors
Cellular and Organismal Processes > Cell Physiology > Cell proliferation
Depositing User: Library Staff
Date Deposited: 16 Dec 2008 23:41
Last Modified: 13 May 2010 22:40

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