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An IKKα-Nucleophosmin Axis Utilizes Inflammatory Signaling to Promote Genome Integrity
- Source :
- Cell Reports, Vol 5, Iss 5, Pp 1243-1255 (2013)
- Publication Year :
- 2013
- Publisher :
- Elsevier, 2013.
-
Abstract
- The inflammatory microenvironment promotes skin tumorigenesis. However, the mechanisms of how cells protect themselves from inflammatory signals have yet to be revealed. Downregulation of IKKα promotes skin tumor progression from papillomas to squamous cell carcinomas, which is frequently accompanied by genomic instability, including aneuploid chromosomes and extra centrosomes. In this study, we found that IKKα promoted oligomerization of nucleophosmin (NPM), a negative centrosome duplication regulator, which further enhanced NPM and centrosome association, inhibited centrosome amplification, and maintained genome integrity. Levels of NPM hexamers and IKKα were conversely associated with skin tumor progression. Importantly, pro-inflammatory cytokine-induced IKKα activation promoted the formation of NPM oligomers and reduced centrosome numbers in mouse and human cells, whereas kinase-dead IKKα blocked this connection. Therefore, our findings suggest a previously unknown mechanism in which an IKKα-NPM axis may use the inflammatory signal to suppress centrosome amplification, promote genomic integrity, and prevent tumor progression.
- Subjects :
- Genome instability
Carcinogenesis
CHO Cells
Biology
medicine.disease_cause
General Biochemistry, Genetics and Molecular Biology
Genomic Instability
Article
Proinflammatory cytokine
03 medical and health sciences
Mice
0302 clinical medicine
Cricetulus
Downregulation and upregulation
Cell Line, Tumor
Cricetinae
medicine
Animals
Humans
Centrosome duplication
lcsh:QH301-705.5
030304 developmental biology
Centrosome
Inflammation
0303 health sciences
Nucleophosmin
Genome
integumentary system
Nuclear Proteins
Cell biology
I-kappa B Kinase
HEK293 Cells
lcsh:Biology (General)
Tumor progression
030220 oncology & carcinogenesis
Carcinoma, Squamous Cell
Protein Multimerization
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 5
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....5469d0f881c21fd015d425deb8bd0b94