a role for numb in p53 stabilizationp53麻木的稳定作用.pdfVIP

Minireview AA rroollee ffoorr NNuummbb iinn pp5533 ssttaabbiilliizzaattiioonn Stephanie Carter and Karen H Vousden Address: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK. Correspondence: Karen H Vousden. Email: k.vousden@beatson.gla.ac.uk Published: 9 May 2008 Genome BBiioollooggyy 2008, 99::221 (doi:10.1186/gb-2008-9-5-221) The electronic version of this article is the complete one and can be found online at /2008/9/5/221 © 2008 BioMed Central Ltd AAbbssttrraacctt The cell-fate determinant Numb has recently been shown to help activate the tumor suppressor protein p53. Loss of Numb in breast cancers would result, therefore, in both the activation of the potential oncogene Notch and the diminution of tumor suppression by p53. The tumor suppressor protein p53 acts primarily as a trans- required for p53 to induce apoptosis - has also been shown cription factor, inducing the expression of genes involved in to be a common event in breast cancers [9]. A recent study cell-cycle arrest, senescence and apoptosis in response to by Colaluca et al. [10] now shows that the cell-fate cellular stresses [1]. While these growth-inhibitory activities determinant Numb, which is frequently lost in breast of p53 are important in preventing tumor development, they tumors, also plays an important role in the activation of p53. are severely detrimental to normal growth and development. Until now, Numb has most commonly been associated with In unstressed cells, therefore, p53 is kept inactive, mainly negative regulation of signaling from the protein Notch, a through polyubiquitination by the E3 ubiq