BCL2-Associated Athanogene 3 Proteins (BAG3)

Zebrafish BCL2-Associated Athanogene 3 (BAG3) interaction partners

1. expression of the co-chaperone BAG3 and other chaperone-assisted selective autophagy factors was analyzed in the cellular, zebrafish and ky/ky mouse models.

2. This study therefore identifies both BAG3 reduction and autophagy promotion as potential therapies for FLNC(W2710X) myofibrillar myopathy, and identifies protein insufficiency due to sequestration, compounded by impaired autophagy, as the cause.

3. findings showed that the P209L mutation causes BAG3 to aggregate; proposed that the gradual loss of available BAG3(wt) and BAG3(P209L) proteins results in insufficiency leading to myofibrillar disintegration

Human BCL2-Associated Athanogene 3 (BAG3) interaction partners

1. HIV-1 Tat induces autophagy by upregulating BAG3 via NF-kappaB signaling.

2. Results show that unique variants in BAG3 found almost exclusively in individuals of African descent were not associated with the onset of dilated cardiomyopathy (DCM) but were associated with a negative influence on the phenotypic response to the development of DCM and worse outcomes of patients with both ischemic and non-ischemic disease.

3. Dilated cardiomyopathy caused by mutations in BAG3 is characterized by high penetrance in carriers > 40years of age and a high risk of progressive heart failure.

4. The current study revealed that BAG3 did not interact with ISG15, but positively regulated ISG15 expression in pancreatic ductal adenocarcinoma cancer.

5. BAG3 mutation causes adult onset Charcot-Marie-Tooth disease, type 2.

6. BAG3 may have an important role in HGF-mediated cell proliferation and metastasis in gastric cancer through an ERK and Egr1-dependent pathway.

7. BAG3 silencing-mediated correction of F508del-CFTR restores the autophagy pathway, which is defective in F508del-CFTR-expressing cells, likely because of the maladaptive stress response in cystic fibrosis pathophysiology.

8. this is the first Korean patient with BAG3 mutation. We described a BAG3 mutation patient with atypical phenotype of CMT and myopathy, and those are expected to broaden the clinical spectrum of the disease and help to diagnose it.

9. High BAG3 expression is associated with Cervical Cancer Cell Proliferation.

10. This case indicates that rigid spine syndrome and sensory-motor axonal neuropathy are key clinical features of BAG3 mutations that should be considered even without cardiac involvement.

11. BAG3 interaction with HSPB8 promotes spatial sequestration of ubiquitinated proteins. BAG3 mutation P209L in the HSPB8-binding motif deregulated association between BAG3 and SQSTM1 and the KEAP1-Nrf2 signaling axis.

12. BAG3 in particular, and maybe nucleotide exchange factors in general, are a potential Achilles heel of the Hsp70 machinery, where minor malfunctioning results in the entrapment of the whole chaperone complex with disastrous consequences for protein homeostasis.

13. BAG3 overexpression in colorectal cancer can promote tumor proliferation, migration and invasion.

14. There was no association of SNPs in ADRB1, GRK5 and BAG3 genes with Takotsubo cardiomyopathy.

15. These findings provide a molecular basis for understanding of BAG3dependent cell proliferation and survival from the aspect of alteration of gene expression.

16. BAG3 can modulate the levels, localization or activity of its partner proteins, thereby regulating major cell pathways and functions, including apoptosis, autophagy, mechanotransduction, cytoskeleton organisation, motility.

17. Genetic and pharmacological interference with BAG3 is capable to resensitize TNBC cells to treatment.

18. The HSF1-BAG3-Mcl-1 signal axis is critical for protection of mutant KRAS colon cancer cells from AUY922-induced apoptosis.

19. The Hsp70-Bag3 complex therefore functions as an important signaling node that senses proteotoxicity and triggers multiple pathways that control cell physiology, including activation of protein aggregation.

20. study revealed oncogenic roles of BAG3 in chondrosarcoma and provided mechanisms that the BAG3-modulated the expression of RUNX2 through upregulation of beta-catenin.

Mouse (Murine) BCL2-Associated Athanogene 3 (BAG3) interaction partners

1. Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid protein that is found predominantly in the heart.

2. We show that MLP depletion is caused by proteasome action. Moreover, MLP C58G interacts with Bag3 and results in a proteotoxic response in the homozygous knock-in mice, as shown by induction of Bag3 and associated heat shock proteins. In conclusion, the newly generated mouse model provides insights into the underlying disease mechanisms of cardiomyopathy caused by mutations in the non-sarcomeric protein MLP

3. expression of the co-chaperone BAG3 and other chaperone-assisted selective autophagy factors was analyzed in the cellular, zebrafish and ky/ky mouse models.

4. It is a cochaperone that mediates autophagy.

5. Thus, BAG3 is critical for the protein turnover of small HSPs via activation of autophagy in the heart.

6. BAG3 plays a relevant role in regulating SNCA clearance via macroautophagy, and the heat shock protein 70-BAG3-sequestosome 1 complex may be involved in this process.

7. BAG3 directly stabilizes hexokinase 2 mRNA and promotes aerobic glycolysis in pancreatic cancer cells.

8. BAG3 expression is required for neuronal differentiation and migration.

9. interaction between BAG3 and HSP70 is essential for BAG3 to stabilize small heat shock proteins and maintain cardiomyocyte protein homeostasis

10. The spatial regulation of mTORC1 exerted by BAG3 apparently provides the basis for a simultaneous induction of autophagy and protein synthesis to maintain the proteome under mechanical strain.

11. Genetic variation in BAG3 plays an important role in the prevention of ischemic tissue necrosis.

12. The aim of this study was to investigate the possible hemodynamic effects of BAG3 performing both in vitro and in vivo experiments.

13. Our findings that BAG3 is localized at the sarcolemma and t-tubules while modulating myocyte contraction and action potential duration through specific interaction with the beta1-adrenergic receptor and L-type Ca(2+) channel provide novel insight into the role of BAG3 in cardiomyopathies and increased arrhythmia risks in heart failure.

14. molecular association of MyHC and BIS is necessary for MyHC stabilization in skeletal muscle.

15. BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages.

16. Bis is upregulated in astrocytes after hypoxia-ischemia; hypoxia-ischemia induces progressive cell death in the hippocampi of bis-positive mice, while hippocampal neurons are less vulnerable to hypoxia-ischemia in mice that lack Bis.

17. Deletion of the bis gene results in a marked increase in the production of corticosterone that is associated with thymic atrophy.

18. BAG3 and Hsc70 interact with actin capping protein CapZ to maintain myofibrillar integrity under mechanical stress.

19. Results indicate that Bis functions to mediate cellular regulation of the stem cell niche on the vascular compartment.

20. BAG3 alters the interaction between HSP70 and IKKgamma, increasing availability of IKKgamma and protecting it from proteasome-dependent degradation; this, in turn, results in increased NF-kappaB activity and survival