An IKKα-Nucleophosmin axis utilizes inflammatory signaling to promote genome integrity

Xiaojun Xia, Shuang Liu, Zuoxiang Xiao, Feng Zhu, Na Young Song, Ming Zhou, Bigang Liu, Jianjun Shen, Kunio Nagashima, Timothy D. Veenstra, Sandra Burkett, Mahesh Datla, Jami Willette-Brown, Haifa Shen, Yinling Hu

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The inflammatory microenvironment promotes skin tumorigenesis. However, the mechanisms by which cells protect themselves from inflammatory signals are unknown. Downregulation of IKKα promotes skin tumor progression from papillomas to squamous cell carcinomas, which is frequently accompanied bygenomic 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, proinflammatory 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 mechanism in which an IKKα-NPM axis may use inflammatory signals to suppress centrosome amplification, promote genomic integrity, and prevent tumor progression.

Original languageEnglish (US)
Pages (from-to)1243-1255
Number of pages13
JournalCell Reports
Volume5
Issue number5
DOIs
StatePublished - Dec 12 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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