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 Nakaya, N.
Right arrow Articles by Enikolopov, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nakaya, N.
Right arrow Articles by Enikolopov, G.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2007, p. 5430-5444, Vol. 27, No. 15
0270-7306/07/$08.00+0     doi:10.1128/MCB.00551-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

noxin, a Novel Stress-Induced Gene Involved in Cell Cycle and Apoptosis{triangledown}

Naoki Nakaya,1,{dagger} Jill Hemish,1,2,{dagger} Peter Krasnov,1 Sang-Yong Kim,1 Yuri Stasiv,1 Tatyana Michurina,1 Daniel Herman,1 Michail S. Davidoff,3 Ralf Middendorff,4 and Grigori Enikolopov1*

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724,1 Graduate Program in Genetics, SUNY at Stony Brook, Stony Brook, New York 11794,2 Institute of Anatomy, University of Hamburg, 20246 Hamburg, Germany,3 Institute of Anatomy and Cell Biology, Justus Liebig University, 35385 Giessen, Germany4

Received 29 March 2006/ Returned for modification 1 May 2007/ Accepted 12 May 2007

We describe a novel stress-induced gene, noxin, and a knockout mouse line with an inactivated noxin gene. The noxin gene does not have sequelogs in the genome and encodes a highly serine-rich protein with predicted phosphorylation sites for ATM, Akt, and DNA-dependent protein kinase kinases; nuclear localization signals; and a Zn finger domain. noxin mRNA and protein levels are under tight control by the cell cycle. noxin, identified as a nitric oxide-inducible gene, is strongly induced by a wide range of stress signals: {gamma}- and UV irradiation, hydrogen peroxide, adriamycin, and cytokines. This induction is dependent on p53. Noxin accumulates in the nucleus in response to stress and, when ectopically expressed, Noxin arrests the cell cycle at G1; although it also induces p53, the cell cycle arrest function of Noxin is independent of p53 activity. noxin knockout mice are viable and fertile; however, they have an enlarged heart, several altered hematopoietic parameters, and a decreased number of spermatids. Importantly, loss or downregulation of Noxin leads to increased cell death. Our results suggest that Noxin may be a component of the cell defense system: it is activated by various stress stimuli, helps cells to withdraw from cycling, and opposes apoptosis.

* Corresponding author. Mailing address: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724. Phone: (516) 367-8316. Fax: (516) 367-6805. E-mail: enik{at}cshl.edu

{triangledown} Published ahead of print on 21 May 2007.

{dagger} N. Nakaya and J. Hemish contributed equally to this study.

Molecular and Cellular Biology, August 2007, p. 5430-5444, Vol. 27, No. 15
0270-7306/07/$08.00+0     doi:10.1128/MCB.00551-06
Copyright © 2007, 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»