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PMID:17515607

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Citation

Nakaya, N, Hemish, J, Krasnov, P, Kim, SY, Stasiv, Y, Michurina, T, Herman, D, Davidoff, MS, Middendorff, R and Enikolopov, G (2007) noxin, a novel stress-induced gene involved in cell cycle and apoptosis. Mol. Cell. Biol. 27:5430-44

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.

Links

PubMed PMC1952090 Online version:10.1128/MCB.00551-06

Keywords

Amino Acid Sequence; Animals; Apoptosis/drug effects; Carrier Proteins/chemistry; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Cycle/drug effects; Cloning, Molecular; Down-Regulation/drug effects; Fibroblasts/drug effects; Fibroblasts/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; Phosphoproteins/genetics; Phosphoproteins/metabolism; RNA, Messenger/genetics; RNA, Messenger/metabolism; S-Nitroso-N-Acetylpenicillamine/pharmacology; Subcellular Fractions/metabolism; Tumor Suppressor Protein p53/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:P53

acts_upstream_of_or_within

GO:0007346: regulation of mitotic cell cycle

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CDN1A

acts_upstream_of_or_within

GO:0007346: regulation of mitotic cell cycle

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DDIAS

acts_upstream_of_or_within

GO:0030097: hemopoiesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DDIAS

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:DDIAS

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:DDIAS

acts_upstream_of_or_within

GO:0007286: spermatid development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000018)

Seeded From UniProt

complete

MOUSE:DDIAS

acts_upstream_of_or_within

GO:0006974: cellular response to DNA damage stimulus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:DDIAS

acts_upstream_of_or_within

GO:2000270: negative regulation of fibroblast apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • regulates_o_occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:DDIAS

acts_upstream_of_or_within

GO:0051726: regulation of cell cycle

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DDIAS

acts_upstream_of_or_within

GO:0071480: cellular response to gamma radiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:DDIAS

acts_upstream_of_or_within

GO:0071447: cellular response to hydroperoxide

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:DDIAS

acts_upstream_of_or_within

GO:0071345: cellular response to cytokine stimulus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:DDIAS

acts_upstream_of_or_within

GO:0034644: cellular response to UV

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • occurs_in:(CL:0000057)

Seeded From UniProt

complete

MOUSE:P53

acts_upstream_of_or_within

GO:0071850: mitotic cell cycle arrest

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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