BACKGROUND AND PURPOSE: Proteasome inhibitors exhibit cytotoxic against tumours of different histology. However, the mechanism of apoptosis induction by these compounds remains unclear and is likely to be a complex cascade of events. Bcl-2-associated athanogene (BAG) family proteins are characterized by their property of interaction with a variety of partners involved in modulating the proliferation/death balance, including heat shock proteins (HSP), Bcl-2, Raf-1. The role of BAG family proteins in proteasome inhibition has not been elucidated. EXPERIMENTAL APPROACH: Effects of proteasome inhibitors on BAG2 expression were evaluated using real-time reverse transcription-polymerase chain reaction (RT-PCR). BAG2 expression was knocked down by small interfering RNAs (siRNA). Cell death was evaluated using Annexin V/propidium iodide staining and subsequent FACS. KEY RESULTS: The proteasome inhibitors, MG132, PSI, lactacystin and epoxomicin, induced BAG2 at the transcriptional level. MG132-induced apoptosis was significantly suppressed by BAG2 knockdown using RNA interference. CONCLUSIONS AND IMPLICATIONS: Our results suggest that BAG2 is a novel molecule induced by proteasome inhibition, which exhibits a pro-apoptotic property in death of thyroid cancer cells induced by proteasome inhibition.
BACKGROUND AND PURPOSE: Proteasome inhibitors exhibit cytotoxic against tumours of different histology. However, the mechanism of apoptosis induction by these compounds remains unclear and is likely to be a complex cascade of events. Bcl-2-associated athanogene (BAG) family proteins are characterized by their property of interaction with a variety of partners involved in modulating the proliferation/death balance, including heat shock proteins (HSP), Bcl-2, Raf-1. The role of BAG family proteins in proteasome inhibition has not been elucidated. EXPERIMENTAL APPROACH: Effects of proteasome inhibitors on BAG2 expression were evaluated using real-time reverse transcription-polymerase chain reaction (RT-PCR). BAG2 expression was knocked down by small interfering RNAs (siRNA). Cell death was evaluated using Annexin V/propidium iodide staining and subsequent FACS. KEY RESULTS: The proteasome inhibitors, MG132, PSI, lactacystin and epoxomicin, induced BAG2 at the transcriptional level. MG132-induced apoptosis was significantly suppressed by BAG2 knockdown using RNA interference. CONCLUSIONS AND IMPLICATIONS: Our results suggest that BAG2 is a novel molecule induced by proteasome inhibition, which exhibits a pro-apoptotic property in death of thyroid cancer cells induced by proteasome inhibition.
Authors: M F Romano; M Festa; G Pagliuca; R Lerose; R Bisogni; F Chiurazzi; G Storti; S Volpe; S Venuta; M C Turco; A Leone Journal: Cell Death Differ Date: 2003-03 Impact factor: 15.828
Authors: M Selmansberger; A Feuchtinger; L Zurnadzhy; A Michna; J C Kaiser; M Abend; A Brenner; T Bogdanova; A Walch; K Unger; H Zitzelsberger; J Hess Journal: Oncogene Date: 2014-10-06 Impact factor: 9.867
Authors: Francesca Galdiero; Anna Maria Bello; Anna Spina; Anna Capiluongo; Sophie Liuu; Margot De Marco; Alessandra Rosati; Mario Capunzo; Maria Napolitano; Emilia Vuttariello; Mario Monaco; Daniela Califano; Maria Caterina Turco; Gennaro Chiappetta; Joëlle Vinh; Giovanni Chiappetta Journal: Oncotarget Date: 2018-01-03