Expression and Subcellular Localization of Inhibitor of Apoptosis (IAP) Proteins in Human Tissues: Mechanisms and Clinical Implications

Apoptosis is a specific gene-controlled type of cell death, involved in the regulation of tissue homeostasis, and, once altered, leading to different pathologic conditions, such as cancer. An increasing body of evidence suggests a role of inhibitor of apoptosis (IAP) proteins in tumor progression, because of their main function as inhibitors of apoptosis in cancer cell models. Ways to exploit the experimental knowledge on IAP proteins for the clinical management of cancer patients are currently being explored. The first part of this thesis deals with the molecular characterization of the mechanisms determining the localization of the best known members of the family of IAP proteins, a specific aspect of IAPs regulation which has been so far largely overlooked.we report that cIAP1 and cIAP2, but not XIAP, are nuclear shuttling proteins, whose subcellular localization is mediated by the CRM1-dependent nuclear export pathway. In the second part of this thesis we investigate the clinical implications of different IAPs localization in cancer and normal cells, and we show how the assessment of IAP proteins localization in tumor tissue samples (especially NSCLC) could be relevant for the management of cancer patients.Giaccone, G. [Promotor]Rodriguez, J. [Copromotor