Induction of BAG2 protein during proteasome inhibitor‐induced apoptosis in thyroid carcinoma cells

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. British Journal of Pharmacology (2008) 155, 655–660; doi:10.1038/bjp.2008.302; published online 28 July 2008