Accession Number : AD1002582


Title :   The Contribution of Prohibitin 1 to Prostate Cancer Chemoresistance


Descriptive Note : Technical Report,29 Sep 2014,28 Sep 2015


Corporate Author : Childrens Hospital Corporation Boston United States


Personal Author(s) : Xu,Yingjie


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=AD1002582


Report Date : 01 Oct 2015


Pagination or Media Count : 76


Abstract : Prohibitin 1 (PHB1) is a member of a highly conserved eukaryotic protein family containing the stomatin/prohibitin/flotillin/HflK/C(SPFH) domain. PHB1 has been functionally linked to diverse cellular processes, including cell-cycle progression, apoptosis, mitochondrial biogenesis and tumor chemoresistance. To better understand the role of PHB1, we performed proteomic experiments to identify the PHB1 interactome and identified the X-linked inhibitor of apoptosis protein (XIAP) as a novel PHB1-interacting protein. The interaction was confirmed by GST pull-down assay, showing a direct interaction between the two proteins. The interaction is functionally significant, as silencing PHB1 decreases XIAP stability, resulting in consequent activation of apoptotic pathway members and restoration of paclitaxel sensitivity. Using deletion constructs of XIAP, we showed that PHB1 binds principally to the BIR3 domain of XIAP. These results suggest that the natural interaction of PHB1 and XIAP represents a novel mechanism for suppression of apoptosis that modulates tumor expansion and the response to chemotherapeutic agents.


Descriptors :   prostate cancer , cancer research , Apoptosis , proteins , neoplasms , BIOASSAY , ANTINEOPLASTIC AGENTS


Distribution Statement : APPROVED FOR PUBLIC RELEASE