The transcriptional repressor dMnt is a regulator of growth in Drosophila melanogaster.
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.
Loo
Lenora W M
LW
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Secombe
Julie
J
Little
John T
JT
Carlos
Leni-Sue
LS
Yost
Cynthia
C
Cheng
Pei-Feng
PF
Flynn
Erin M
EM
Edgar
Bruce A
BA
Eisenman
Robert N
RN
D000483:Alleles; D017398:Alternative Splicing; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D049628:Body Size; D049109:Cell Proliferation; D002469:Cell Separation; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D019281:Dimerization; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000254:growth & development* / Q000502:physiology; D005434:Flow Cytometry; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D008136:Longevity; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D007328:Insulin; C112506:MAD protein, Drosophila; C106465:MNT protein, human; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D004247:DNA; D005982:Glutathione Transferase