An IKK alpha-Nucleophosmin Axis Utilizes Inflammatory Signaling to Promote Genome Integrity

作者：Xia Xiaojun; Liu Shuang; Xiao Zuoxiang; Zhu Feng; Song Na Young; Zhou Ming; Liu Bigang; Shen Jianjun; Nagashima Kunio; Veenstra Timothy D; Burkett Sandra; Datla Mahesh; Willette Brown Jami; Shen Haifa; Hu Yinling^*

来源：Cell Reports, 2013, 5(5): 1243-1255.

DOI：10.1016/j.celrep.2013.10.046

The inflammatory microenvironment promotes skin tumorigenesis. However, the mechanisms by which cells protect themselves from inflammatory signals are unknown. Downregulation of IKK alpha 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 IKK alpha 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 IKK alpha were conversely associated with skin tumor progression. Importantly, proinflammatory cytokine-induced IKK alpha activation promoted the formation of NPM oligomers and reduced centrosome numbers in mouse and human cells, whereas kinase-dead IKK alpha blocked this connection. Therefore, our findings suggest a mechanism in which an IKK alpha-NPM axis may use inflammatory signals to suppress centrosome amplification, promote genomic integrity, and prevent tumor progression.

• 出版日期2013-12