title: BAG3 down-modulation sensitizes HPV18(+) HeLa cells to PEITC-induced apoptosis and restores p53.
abstract: BAG3 is a multi-functional component of tumor cell pro-survival machinery, and its biological functions have been largely associated to proteasome system. Here, we show that BAG3 down-modulation resulted in reduced cell viability and enhanced PEITC-induced apoptosis largely more extensively in HeLa (HPV18(+)) rather than in C33A (HPV(-)) cervical carcinoma cell lines. Moreover, we demonstrate that BAG3 suppression led to a decrease of viral E6 oncoprotein and a concomitant recovery of p53 tumor suppressor, the best recognized target of E6 for proteasome degradation. E6 and p53 expression were modulated at protein level, since their respective mRNAs were unaffected. Taken together our findings reveal a novel role for BAG3 as host protein contributing to HPV18 E6-activated pro-survival strategies, and suggest a possible relevance of its expression levels in drug/radiotherapy-resistance of HPV18-bearing cervical carcinomas.
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II n.132, Fisciano, 84084, Salerno, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cotugno
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II n.132, Fisciano, 84084, Salerno, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Basile
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II n.132, Fisciano, 84084, Salerno, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Romano
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II n.132, Fisciano, 84084, Salerno, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Gallotta
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II n.132, Fisciano, 84084, Salerno, Italy. Electronic address: mabelisa@unisa.it.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Belisario
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006367:HeLa Cells; D052161:Human papillomavirus 18; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000821:virology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D017879:Isothiocyanates; D009856:Oncogene Proteins, Viral; D034741:RNA, Small Interfering; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C058305:phenethyl isothiocyanate; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases
keywords: BAG3; E6; HPV18; HeLa cells; PEITC; p53