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Molecular and Cellular Biology, August 2005, p. 7078-7091, Vol. 25, No. 16
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.16.7078-7091.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Transcriptional Repressor dMnt Is a Regulator of Growth in Drosophila melanogaster{dagger}

Lenora W. M. Loo,{ddagger} Julie Secombe,{ddagger} John T. Little, Leni-Sue Carlos, Cynthia Yost, Pei-Feng Cheng, Erin M. Flynn, Bruce A. Edgar, and Robert N. Eisenman*

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington

Received 4 May 2005/ Returned for modification 22 May 2005/ Accepted 27 May 2005

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.

* Corresponding author. Mailing address: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., P.O. Box 19024, Seattle, WA 98109-1024. Phone: (206) 667-4445. Fax: (206) 667-6522. E-mail: eisenman{at}fhcrc.org.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Both authors contributed equally to this work.

Molecular and Cellular Biology, August 2005, p. 7078-7091, Vol. 25, No. 16
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.16.7078-7091.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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