Nakaya, N., Hemish, J., Krasnov, P., Kim, S. Y., Stasiv, Y., Michurina, T. V., Herman, D., Davidoff, M. S., Middendorff, R., Enikolopov, G. N. (August 2007) noxin, a novel stress-induced gene involved in cell cycle and apoptosis. Mol Cell Biol, 27 (15). pp. 5430-44. ISSN 0270-7306 (Print)
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Abstract
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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Amino Acid Sequence Animals Apoptosis/drug effects Carrier Proteins/chemistry/ genetics/metabolism Cell Cycle/drug effects Cloning, Molecular Down-Regulation/drug effects Fibroblasts/drug effects/metabolism Gene Expression Profiling Gene Targeting Mice Mice, Knockout Molecular Sequence Data NIH 3T3 Cells Nitric Oxide/pharmacology Organ Size/drug effects Phenotype Phosphoproteins/chemistry/ genetics/metabolism RNA, Messenger/genetics/metabolism S-Nitroso-N-Acetylpenicillamine/pharmacology Subcellular Fractions/metabolism Tumor Suppressor Protein p53/genetics |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > zinc finger proteins |
| CSHL Authors: | |
| Communities: | CSHL labs > Enikopolov lab |
| Depositing User: | CSHL Librarian |
| Date: | August 2007 |
| Date Deposited: | 10 Nov 2011 15:42 |
| Last Modified: | 28 Feb 2017 22:04 |
| PMCID: | PMC1952090 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/23105 |
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