Autoregulation of co-chaperone BAG3 gene transcription.
The Bcl-2-associated athanogene, BAG, protein family through their BAG domain associates with the heat shock protein 70 (HSP-70) and modulates its chaperone activity. One member of this family, BAG3, appears to play an important role in protein homeostasis, as its expression promotes cell survival. Expression of BAG3 is enhanced by a variety of stress-inducing agents. Here we describe a role for BAG3 to modulate transcription of its own promoter through a positive feedback loop involving its 5'-UTR sequence. Activation of the BAG3 promoter is mediated by the BAG domain and is independent of BAG3 association with the UTR sequence. Autoactivation of the BAG3 gene is observed in several cultures of human glial cells including gliomas, but not in several other non-glial cell lines such as He La and others. Results from cell fractionation and immunocytochemistry showed BAG3 in the cytoplasm as well as the nuclei of glial cells. These observations suggest that BAG3 gene expression is controlled by its own product and that this may be critical for the biological activity of BAG3 in some cell types.
Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 1900 North 12th Street, Philadelphia, Pennsylvania 19122, USA.
Antonio
A
Gentilella
Kamel
K
Khalili
D020121:5' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000378:metabolism / Q000648:ultrastructure; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D015533:Transcriptional Activation; D015854:Up-Regulation
D020121:5' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D018832:Molecular Chaperones