caa a22 4500 467905584 CHVBK 20180406152833.0 cr unu---uuuuu 170328e20060901xx s 000 0 eng 10.1007/s10735-006-9040-y doi (NATIONALLICENCE)springer-10.1007/s10735-006-9040-y Gjerset Ruth Sidney Kimmel Cancer Center, 10835 Road to the Cure (previously Altman Row), 92121, San Diego, CA, USA aut DNA damage, p14ARF, Nucleophosmin (NPM/B23), and cancer [Elektronische Daten] [Ruth Gjerset] 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. Springer Science+Business Media B.V., 2006 p53 nationallicence p14ARF nationallicence DNA damage nationallicence NPM nationallicence Nucleophosmin nationallicence B23 nationallicence Nucleolus nationallicence Journal of Molecular Histology Kluwer Academic Publishers 37/5-7(2006-09-01), 239-251 1567-2379 37:5-7<239 2006 37 10735 https://doi.org/10.1007/s10735-006-9040-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10735-006-9040-y text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Gjerset Ruth Sidney Kimmel Cancer Center, 10835 Road to the Cure (previously Altman Row), 92121, San Diego, CA, USA aut NATIONALLICENCE 773 0- Journal of Molecular Histology Kluwer Academic Publishers 37/5-7(2006-09-01), 239-251 1567-2379 37:5-7<239 2006 37 10735 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer