| First Author | Xia X | Year | 2013 |
| Journal | Cell Rep | Volume | 5 |
| Issue | 5 | Pages | 1243-55 |
| PubMed ID | 24290756 | Mgi Jnum | J:204153 |
| Mgi Id | MGI:5529727 | Doi | 10.1016/j.celrep.2013.10.046 |
| Citation | Xia X, et al. (2013) An IKKalpha-Nucleophosmin Axis Utilizes Inflammatory Signaling to Promote Genome Integrity. Cell Rep 5(5):1243-55 |
| abstractText | The inflammatory microenvironment promotes skin tumorigenesis. However, the mechanisms by which cells protect themselves from inflammatory signals are unknown. Downregulation of IKKalpha 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 IKKalpha 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 IKKalpha were conversely associated with skin tumor progression. Importantly, proinflammatory cytokine-induced IKKalpha activation promoted the formation of NPM oligomers and reduced centrosome numbers in mouse and human cells, whereas kinase-dead IKKalpha blocked this connection. Therefore, our findings suggest a mechanism in which an IKKalpha-NPM axis may use inflammatory signals to suppress centrosome amplification, promote genomic integrity, and prevent tumor progression. |
