This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Papaconstantinou, M.
Right arrow Articles by Bédard, P.-A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Papaconstantinou, M.
Right arrow Articles by Bédard, P.-A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2005, p. 9960-9972, Vol. 25, No. 22
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.22.9960-9972.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Menin Is a Regulator of the Stress Response in Drosophila melanogaster

Maria Papaconstantinou,1 Ying Wu,1 Hendrik Nikolaas Pretorius,1 Nishi Singh,1 Gabriella Gianfelice,2 Robert M. Tanguay,3 Ana Regina Campos,1 and Pierre-André Bédard1*

Department of Biology, McMaster University, Hamilton, Ontario, Canada,1 Department of Biology, York University, Toronto, Ontario, Canada,2 Département de Médecine, Université Laval, Ste-Foy, Québec, Canada3

Received 24 March 2005/ Returned for modification 25 April 2005/ Accepted 17 August 2005

Menin, the product of the multiple endocrine neoplasia type I gene, has been implicated in several biological processes, including the control of gene expression and apoptosis, the modulation of mitogen-activated protein kinase pathways, and DNA damage sensing or repair. In this study, we have investigated the function of menin in the model organism Drosophila melanogaster. We show that Drosophila lines overexpressing menin or an RNA interference for this gene develop normally but are impaired in their response to several stresses, including heat shock, hypoxia, hyperosmolarity and oxidative stress. In the embryo subjected to heat shock, this impairment was characterized by a high degree of developmental arrest and lethality. The overexpression of menin enhanced the expression of HSP70 in embryos and interfered with its down-regulation during recovery at the normal temperature. In contrast, the inhibition of menin with RNA interference reduced the induction of HSP70 and blocked the activation of HSP23 upon heat shock, Menin was recruited to the Hsp70 promoter upon heat shock and menin overexpression stimulated the activity of this promoter in embryos. A 70-kDa inducible form of menin was expressed in response to heat shock, indicating that menin is also regulated in conditions of stress. The induction of HSP70 and HSP23 was markedly reduced or absent in mutant embryos harboring a deletion of the menin gene. These embryos, which did not express the heat shock-inducible form of menin, were also hypersensitive to various conditions of stress. These results suggest a novel role for menin in the control of the stress response and in processes associated with the maintenance of protein integrity.

* Corresponding author. Mailing address: Department of Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4K1. Phone: (905) 525-9140, ext. 23149. Fax: (905) 522-6066. E-mail: abedard{at}mcmaster.ca.

Molecular and Cellular Biology, November 2005, p. 9960-9972, Vol. 25, No. 22
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.22.9960-9972.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»