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Molecular and Cellular Biology, November 2005, p. 9897-9909, Vol. 25, No. 22
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.22.9897-9909.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human c-Myc Isoforms Differentially Regulate Cell Growth and Apoptosis in Drosophila melanogaster

C. Benassayag,¹ L. Montero,^2, N. Colombié,^1,3 P. Gallant,² D. Cribbs,¹ and D. Morello^1*

Centre de Biologie du Développement, CNRS UMR 5547, Université Paul Sabatier, 118 Rte. de Narbonne, 31062 Toulouse Cedex, France,¹ Zoologisches Institut, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland,² Institut de Sciences et Technologies du Médicament de Toulouse, UMR 2587, CNRS-Pierre Fabre, 3 rue des Satellites, 31400 Toulouse, France³

Received 28 February 2005/ Returned for modification 8 April 2005/ Accepted 15 July 2005

The human c-myc proto-oncogene, implicated in the control of many cellular processes including cell growth and apoptosis, encodes three isoforms which differ in their N-terminal region. The functions of these isoforms have never been addressed in vivo. Here, we used Drosophila melanogaster to examine their functions in a fully integrated system. First, we established that the human c-Myc protein can rescue lethal mutations of the Drosophila myc ortholog, dmyc, demonstrating the biological relevance of this model. Then, we characterized a new lethal dmyc insertion allele, which permits expression of human c-Myc in place of dMyc and used it to compare physiological activities of these isoforms in whole-organism rescue, transcription, cell growth, and apoptosis. These isoforms differ both quantitatively and qualitatively. Most remarkably, while the small c-MycS form truncated for much of its N-terminal trans-activation domain efficiently rescued viability and cell growth, it did not induce detectable programmed cell death. Our data indicate that the main functional difference between c-Myc isoforms resides in their apoptotic properties and that the N-terminal region, containing the conserved MbI motif, is decisive in governing the choice between growth and death.

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* Corresponding author. Mailing address: Centre de Biologie du Développement, CNRS UMR 5547, Université Paul Sabatier, 118 Rte. de Narbonne, 31062 Toulouse Cedex, France. Phone: (33) 561 55 64 73. Fax: (33) 561 55 65 07. E-mail: morello{at}cict.fr.

Present address: Gema Biotech S.A., Marcelo T. de Alvear 2289 1122, Buenos Aires, Argentina.

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Molecular and Cellular Biology, November 2005, p. 9897-9909, Vol. 25, No. 22
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.22.9897-9909.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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