Journal of Molecular Histology

, Volume 37, Issue 5–7, pp 239–251 | Cite as

DNA damage, p14ARF, Nucleophosmin (NPM/B23), and cancer

  • Ruth A. GjersetEmail author
Original paper


The p53/p14ARF/mdm2 stress response pathway plays a central role in mediating cellular responses to oncogene activation, genome instability, and therapy-induced DNA damage. Abrogation of the pathway occurs in most if not all cancers, and may be essential for tumor development. The high frequency with which the pathway is disabled in cancer and the fact that the pathway appears to be incompatible with tumor cell growth, has made it an important point of focus in cancer research and therapeutics development. Recently, Nucleophosmin (NPM, B23, NO38 and numatrin), a multifunctional nucleolar protein, has emerged as a p14ARF binding protein and regulator of p53. While complex formation between ARF and NPM retains ARF in the nucleolus and prevents ARF from activating p53, DNA damaging treatments promote a transient subnuclear redistribution of ARF to the nucleoplasm, where it interacts with mdm2 and promotes p53 activation. The results add support to a recently proposed model in which the nucleolus serves as a p53-uspstream sensor of stress, and where ARF links nucleolar stress signals to nucleoplasmic effectors of the stress response. A better understanding of ARF’s nucleolar interactions could further elucidate the regulation of the p53 pathway and suggest new therapeutic approaches to restore p53 function.


p53 p14ARF DNA damage NPM Nucleophosmin B23 Nucleolus 


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Our laboratory is supported by the NCI/NIH (CA111868) and the California Tobacco-Related Disease Research Program (11RT-0074). We apologize to the many authors who we were unable to cite due to space limitations.


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Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  1. 1.Sidney Kimmel Cancer CenterSan DiegoUSA

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