BAG3: Nature’s Quintessential Multi-Functional Protein Functions as a Ubiquitous Intra-Cellular Glue
Caitlyn M. Brenner,
Muaaz Choudhary,
Michael G. McCormick,
David Cheung,
Gavin P. Landesberg,
Ju-Fang Wang,
Jianliang Song,
Thomas G. Martin,
Joseph Y. Cheung,
Hui-Qi Qu,
Hakon Hakonarson,
Arthur M. Feldman
Affiliations
Caitlyn M. Brenner
Department of Medicine, Division of Cardiology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, MERB 752, Philadelphia, PA 19140, USA
Muaaz Choudhary
Department of Medicine, Division of Cardiology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, MERB 752, Philadelphia, PA 19140, USA
Michael G. McCormick
Department of Medicine, Division of Cardiology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, MERB 752, Philadelphia, PA 19140, USA
David Cheung
Department of Medicine, Division of Cardiology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, MERB 752, Philadelphia, PA 19140, USA
Gavin P. Landesberg
Department of Medicine, Division of Cardiology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, MERB 752, Philadelphia, PA 19140, USA
Ju-Fang Wang
Department of Medicine, Division of Cardiology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, MERB 752, Philadelphia, PA 19140, USA
Jianliang Song
Department of Medicine, Division of Cardiology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, MERB 752, Philadelphia, PA 19140, USA
Thomas G. Martin
Department of Molecular, Cellular and Developmental Biology, Colorado University School of Medicine, Aurora, CO 80045, USA
Joseph Y. Cheung
Division of Renal Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Hui-Qi Qu
Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 191104, USA
Hakon Hakonarson
Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 191104, USA
Arthur M. Feldman
Department of Medicine, Division of Cardiology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, MERB 752, Philadelphia, PA 19140, USA
BAG3 is a 575 amino acid protein that is found throughout the animal kingdom and homologs have been identified in plants. The protein is expressed ubiquitously but is most prominent in cardiac muscle, skeletal muscle, the brain and in many cancers. We describe BAG3 as a quintessential multi-functional protein. It supports autophagy of both misfolded proteins and damaged organelles, inhibits apoptosis, maintains the homeostasis of the mitochondria, and facilitates excitation contraction coupling through the L-type calcium channel and the beta-adrenergic receptor. High levels of BAG3 are associated with insensitivity to chemotherapy in malignant cells whereas both loss of function and gain of function variants are associated with cardiomyopathy.
