Overexpression of mouse Mdm2 induces developmental phenotypes in Drosophila

Adriana Folberg-Blum; Amir Sapir; Ben Zion Shilo; Moshe Oren

doi:10.1038/sj.onc.1205305

Overexpression of mouse Mdm2 induces developmental phenotypes in Drosophila

Adriana Folberg-Blum, Amir Sapir, Ben Zion Shilo, Moshe Oren

Research output: Contribution to journal › Article › peer-review

Abstract

The Mdm2 proto-oncogene is amplified and over-expressed in a variety of tumors. One of the major functions of Mdm2 described to date is its ability to modulate the levels and activity of the tumor suppressor protein p53. Mdm2 binds to the N-terminus of p53 and, through its action as an E3 ubiquitin ligase, targets p53 for rapid proteasomal degradation. Mdm2 can also bind to other cellular proteins such as hNumb, E2F1, Rb and Akt; however, the biological significance of these interactions is less clear. To gain insight into the function of Mdm2 in vivo, we have generated a transgenic Drosophila strain bearing the mouse Mdm2 gene. Ectopic expression of Mdm2, using the UAS/GAL4 system, causes eye and wing phenotypes in the fly. Analysis of wing imaginal discs from third instar larvae showed that expression of Mdm2 induces apoptosis. Crosses did not reveal genetic interactions between Mdm2 and the Drosophila homolog of E2F, Numb and Akt. These transgenic flies may provide a unique experimental model for exploring the molecular interactions of Mdm2 in a developmental context.

Original language	English
Pages (from-to)	2413-2417
Number of pages	5
Journal	Oncogene
Volume	21
Issue number	15
DOIs	https://doi.org/10.1038/sj.onc.1205305
State	Published - 4 Apr 2002
Externally published	Yes

Bibliographical note

Funding Information:
We thank H Steller, E Schejter, T Volk and L Glazer for stimulating discussions and valuable advice. We are grateful to Idun Pharmaceuticals for the CM1 antibody, and to Y Jan, A Manoukian, W Du, H Steller, Exelixis Inc., and the Bloomington Stock Center for generously providing fly strains. We would like to thank the members of the Shilo and Oren labs for their support and advice throughout this work. This work was supported in part by grant RO1 CA 40099 from the National Cancer Institute and by Yad Abraham Center for Cancer Diagnosis and Therapy. A Folberg-Blum was recipient of a Clore Post-Doctoral Fellowship from the Weizmann Institute of Science throughout this work.

Keywords

Apoptosis
Drosophila
Mdm2

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

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10.1038/sj.onc.1205305

Cite this

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title = "Overexpression of mouse Mdm2 induces developmental phenotypes in Drosophila",

abstract = "The Mdm2 proto-oncogene is amplified and over-expressed in a variety of tumors. One of the major functions of Mdm2 described to date is its ability to modulate the levels and activity of the tumor suppressor protein p53. Mdm2 binds to the N-terminus of p53 and, through its action as an E3 ubiquitin ligase, targets p53 for rapid proteasomal degradation. Mdm2 can also bind to other cellular proteins such as hNumb, E2F1, Rb and Akt; however, the biological significance of these interactions is less clear. To gain insight into the function of Mdm2 in vivo, we have generated a transgenic Drosophila strain bearing the mouse Mdm2 gene. Ectopic expression of Mdm2, using the UAS/GAL4 system, causes eye and wing phenotypes in the fly. Analysis of wing imaginal discs from third instar larvae showed that expression of Mdm2 induces apoptosis. Crosses did not reveal genetic interactions between Mdm2 and the Drosophila homolog of E2F, Numb and Akt. These transgenic flies may provide a unique experimental model for exploring the molecular interactions of Mdm2 in a developmental context.",

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note = "Funding Information: We thank H Steller, E Schejter, T Volk and L Glazer for stimulating discussions and valuable advice. We are grateful to Idun Pharmaceuticals for the CM1 antibody, and to Y Jan, A Manoukian, W Du, H Steller, Exelixis Inc., and the Bloomington Stock Center for generously providing fly strains. We would like to thank the members of the Shilo and Oren labs for their support and advice throughout this work. This work was supported in part by grant RO1 CA 40099 from the National Cancer Institute and by Yad Abraham Center for Cancer Diagnosis and Therapy. A Folberg-Blum was recipient of a Clore Post-Doctoral Fellowship from the Weizmann Institute of Science throughout this work.",

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N2 - The Mdm2 proto-oncogene is amplified and over-expressed in a variety of tumors. One of the major functions of Mdm2 described to date is its ability to modulate the levels and activity of the tumor suppressor protein p53. Mdm2 binds to the N-terminus of p53 and, through its action as an E3 ubiquitin ligase, targets p53 for rapid proteasomal degradation. Mdm2 can also bind to other cellular proteins such as hNumb, E2F1, Rb and Akt; however, the biological significance of these interactions is less clear. To gain insight into the function of Mdm2 in vivo, we have generated a transgenic Drosophila strain bearing the mouse Mdm2 gene. Ectopic expression of Mdm2, using the UAS/GAL4 system, causes eye and wing phenotypes in the fly. Analysis of wing imaginal discs from third instar larvae showed that expression of Mdm2 induces apoptosis. Crosses did not reveal genetic interactions between Mdm2 and the Drosophila homolog of E2F, Numb and Akt. These transgenic flies may provide a unique experimental model for exploring the molecular interactions of Mdm2 in a developmental context.

AB - The Mdm2 proto-oncogene is amplified and over-expressed in a variety of tumors. One of the major functions of Mdm2 described to date is its ability to modulate the levels and activity of the tumor suppressor protein p53. Mdm2 binds to the N-terminus of p53 and, through its action as an E3 ubiquitin ligase, targets p53 for rapid proteasomal degradation. Mdm2 can also bind to other cellular proteins such as hNumb, E2F1, Rb and Akt; however, the biological significance of these interactions is less clear. To gain insight into the function of Mdm2 in vivo, we have generated a transgenic Drosophila strain bearing the mouse Mdm2 gene. Ectopic expression of Mdm2, using the UAS/GAL4 system, causes eye and wing phenotypes in the fly. Analysis of wing imaginal discs from third instar larvae showed that expression of Mdm2 induces apoptosis. Crosses did not reveal genetic interactions between Mdm2 and the Drosophila homolog of E2F, Numb and Akt. These transgenic flies may provide a unique experimental model for exploring the molecular interactions of Mdm2 in a developmental context.

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Overexpression of mouse Mdm2 induces developmental phenotypes in Drosophila

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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