Guest post by Kate Campion
Bcl2-associated athanogene (BAG3) (also known as CAIR-1) is a pleiotropic co-chaperone protein that is capable of activating multiple intracellular pathways. First identified as an anti-apoptotic protein, BAG3 has since been implicated in protein degradation via chaperone-mediated autophagy, CNS development, muscular dystrophies and neuropathies, the progress of viral infections, adhesion and migration, and cancer cell survival.
The BAG3 protein may also be of significance to research into neurodegenertion. Disruption to protein degradation pathways is known to contribute to diseases such as Parkinson’s, Alzheimer’s and Huntington’s. Interestingly, BAG3 is expressed in astrocytes in individuals with these conditions and facilitates clearance of protein aggregation during astrocytosis ― a response to CNS destruction . Although a firm link to these diseases has not been established, BAG3 may represent a possible therapeutic target to inhibit disease progression during the early stages of neurodegenerative disease .
Work with Proteintech’s BAG3 antibody
There is evidence that mutated BAG3 causes a severe type of childhood muscular dystrophy (myofibrillar myopathy). Recent findings published in Nature Genetics support this body of work; the paper identifies this previously unrelated type of muscular dystrophy as a BAG3-related myopathy. Proteintech’s anti-BAG3 antibody was used in this study to examine whether the protein could interact with a mutated co-chaperone called DNAJB6. The antibody enabled the authors to describe the disease-aggravating effect of BAG3 interaction with pathological DNAJB6 in Limb-girdle muscular dystrophy (LGMD1D), suggesting a direct role for BAG3 in the pathomechanism of this disease .
Proteintech’s BAG3 antibody has also been utilized in work examining the function of BAG3 in response to viral infection. A recent paper examines the role of BAG3 in response to glial cell infection with JC virus (JCV), an infective agent known to possess oncogenic activity and also cause the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). With the Proteintech BAG3 antibody, the authors were able to show that BAG3 decreases viral expression of the large T‑antigen (T-Ag) protein, which gives the virus its malignant potential. BAG3 elicits its anti-T-Ag effects through induction of the oncogenic protein’s autophagic degradation . In light of BAG3 playing a role in response to HIV-1 infection [4 and 5], such investigations demonstrate how BAG3 might play an important role in cellular response to viral infection through its involvement in apoptotic and autophagic processes.
Further applications of Proteintech’s BAG3 antibody
Proteintech’s BAG3 antibody (Catalog number 10599-1-AP) has also been employed to investigate both physiological and pathological BAG3 gene expression, the role of BAG3 in antigen processing, and aggresome targeted degradation via the dynein motor complex. The BAG3 antibody can be used for a number of applications including Western blotting, immunoprecipitation, immunohistochemistry and immunofluorescence.
BAG3 protein levels impact on apoptotic events in microglial cells harbouring HIV-1 virus. Previously, the authors had discovered BAG3 expression increased upon infection with HIV-1 , and subsequently when its expression was knocked down during these conditions in microglial cells, a marked increase in apoptosis was seen. After further investigation, the authors concluded that BAG3 protein induction counteracts cell stress and apoptotic events induced by HIV-1 infection .
Guest Blogger Profile
Katherine Campion is in the final year of her Physiology PhD at the University of Manchester, investigating the cell biology of calcium homeostasis and associated pathologies. Katherine has also spent time at Böhringer-Ingelheim in Vienna researching cancer signaling pathways. She is a published author in peer-reviewed journals and her work has received award at the 2010 Rank Prize Fund mini-symposia.