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

Abstract

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.

MicroRNA-27b Modulates Inflammatory Response and Apoptosis duringMycobacterium tuberculosisInfection

“…Bag2 is a member of the BAG family that is characterized by the BAG domain. As a group of multipurpose proteins, Bag2 is linked with various transcription factors and administrates a series of intracellular courses (43,44); however, no precise function of Bag2 has been reported in the host defense mechanism against M. tuberculosis. Our study validates Bag2 as a critical target of miR-27b and shows that the activity of the Bag2 39-UTR reporter plasmid is suppressed in the presence of a miR-27b mimic during infection.…”

Microarray expression profiles of genes in lung tissues of rats subjected to focal cerebral ischemia-induced lung injury following bone marrow-derived mesenchymal stem cell transplantation

“…It is mainly involved in the degration of intracellular proteins. Wang et al (62) reported that in thyroid cancer, the expression of BAG-2 promotes apoptosis in vitro and its apoptotic activity can be induced by proteasome inhibitor. Thus, the BMSC transplantation can improve behavioral and lung function following permanent focal cerebral ischemia, associated with the participation of multiple genes and signaling pathways.…”

BAG2 Promotes Proliferation and Metastasis of Gastric Cancer via ERK1/2 Signaling and Partially Regulated by miR186

“…It has been reported that high expression of BAG2 can induce p21-dependent aging and subsequent carcinogenic stagnation (9). It also has been shown that BAG2 can promote apoptosis in thyroid cancer in response to proteasome inhibitors (10). However, in recent years, further studies have shown that BAG2 plays a pivotal role as an oncogene.…”