NUMB controls p53 tumour suppressor activity

Ivan N. Colaluca, Daniela Tosoni, Paolo Nuciforo, Francesca Senic-Matuglia, Viviana Galimberti, Giuseppe Viale, Salvatore Pece () and Pier Paolo Di Fiore ()
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Ivan N. Colaluca: IFOM, the FIRC Institute for Molecular Oncology Foundation, Via Adamello 16, 20139, Milan, Italy
Daniela Tosoni: IFOM, the FIRC Institute for Molecular Oncology Foundation, Via Adamello 16, 20139, Milan, Italy
Paolo Nuciforo: IFOM, the FIRC Institute for Molecular Oncology Foundation, Via Adamello 16, 20139, Milan, Italy
Francesca Senic-Matuglia: IFOM, the FIRC Institute for Molecular Oncology Foundation, Via Adamello 16, 20139, Milan, Italy
Viviana Galimberti: European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
Giuseppe Viale: European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
Salvatore Pece: IFOM, the FIRC Institute for Molecular Oncology Foundation, Via Adamello 16, 20139, Milan, Italy
Pier Paolo Di Fiore: IFOM, the FIRC Institute for Molecular Oncology Foundation, Via Adamello 16, 20139, Milan, Italy

Nature, 2008, vol. 451, issue 7174, 76-80

Abstract: NUMB's anticancer action The NUMB protein is involved in cell fate decisions via an interaction with a NOTCH family plasma membrane receptor, and plays a role in endocytosis. Its expression was known to be downregulated in human breast cancers. Now NUMB has been found to act as a tumour suppressor protein by inhibiting the ubiquitin ligase HDM2, thereby preventing the destruction of the major tumour suppressor p53. In addition, low levels of NUMB expression in breast tumours are found to be associated with a poor prognosis. These findings connect two areas of cell biology previously considered unrelated, and are of potential relevance for the design of rational therapies for cancer.

Date: 2008
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DOI: 10.1038/nature06412

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