NUMB controls p53 tumour suppressor activity

NUMB is a cell fate determinant, which, by asymmetrically partitioning at mitosis, controls cell fate choices by antagonising the activity of the plasma membrane receptor of the NOTCH family. NUMB is also an endocytic protein, and the NOTCH-NUMB counteraction has been linked to this function. There might be, however, additional functions of NUMB, as witnessed by its proposed role as a tumour suppressor in breast cancer. Here we describe a previously unknown function for human NUMB as a regulator of tumour protein p53 (also known as TP53). NUMB enters in a tricomplex with p53 and the E3 ubiquitin ligase HDM2 (also known as MDM2), thereby preventing ubiquitination and degradation of p53. This results in increased p53 protein levels and activity, and in regulation of p53-dependent phenotypes. In breast cancers there is frequent loss of NUMB expression. We show that, in primary breast tumour cells, this event causes decreased p53 levels and increased chemoresistance. In breast cancers, loss of NUMB expression causes increased activity of the receptor NOTCH. Thus, in these cancers, a single event - loss of NUMB expression - determines activation of an oncogene (NOTCH) and attenuation of the p53 tumour suppressor pathway. Biologically, this results in an aggressive tumour phenotype, as witnessed by findings that NUMB-defective breast tumours display poor prognosis. Our results uncover a previously unknown tumour suppressor circuitry

Moving beyond binary opposition: exploring the tapestry of gender in consumer research and marketing

The last two decades have seen an exponential growth in research pertaining to gender issues in marketing and consumer research. This special issue of Marketing Theory, together with the ongoing Association for Consumer Research Gender, Marketing and Consumer Research conference series, now approaching its tenth iteration, demonstrates the continued interest in gender issues in our disciplines. Introducing the special issue, this paper’s remit is threefold: it maps the substantive and theoretical developments of gender research within our discipline; it locates this work on gender within its broader context in humanities and social science; and it introduces the reader to the four papers in this special issue. The paper concludes that gender research has moved from the margins to become a strong body of work within marketing and consumer research. That said, there remains substantive opportunity for further development, where gender and feminist research can offer new insights, critiques, theories and approaches