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BAG3

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Template:PBB BAG family molecular chaperone regulator 3 is a protein that in humans is encoded by the BAG3 gene. BAG3 is involved in chaperone-assisted selective autophagy (CASA).[1][2][3][4][5]

Template:PBB Summary BAG gene has been implicated in age related neurodegenerative diseases such as Alzheimer's. It has been demonstrated that BAG1 and BAG 3 regulate the proteasomal and lysosomal protein elimination pathways, respectively.[6][7] It has also been shown to be the cause of familial dilated cardiomyopathy.[8] That BAG3 mutations are responsible for familial dilated cardiomyopathy is confirmed by another study describing 6 new molecular variants (2 missense and 4 premature Stops ). Moreover, the same publication reported that BAG3 polymorphisms are also associated with sporadic forms of the disease together with HSPB7 locus.[9]

In muscle cells, BAG3 cooperates with the molecular chaperones Hsc70 and HspB8 to induce the degradation of mechanically damaged cytoskeleton components in lysosomes. This process is called chaperone-assisted selective autophagy (CASA) and is essential for maintaining muscle activity in flies, mice and men.[4]

BAG3 is able to stimulate the expression of cytoskeleton proteins in response to mechanical tension by activating the transcription regulators YAP1 and WWTR1.[5] BAG3 balances protein synthesis and protein degradation under mechanical stress.

Interactions

BAG3 has been shown to interact with HSPA8,[1] HSPA1A,[10][11] PLCG1,[10] Dynein,[12] SYNPO2, LATS1, and AMOTL1[5]

References

  1. ^ a b Takayama S, Xie Z, Reed JC (1999). "An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators". J Biol Chem. 274 (2): 781–6. doi:10.1074/jbc.274.2.781. PMID 9873016. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) Cite error: The named reference "pmid9873016" was defined multiple times with different content (see the help page).
  2. ^ Carra S, Seguin SJ, Landry J (2008). "HspB8 and Bag3: a new chaperone complex targeting misfolded proteins to macroautophagy". Autophagy. 4 (2): 237–9. PMID 18094623. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ "Entrez Gene: BAG3 BCL2-associated athanogene 3".
  4. ^ a b Arndt V, Dick N, Tawo R, Dreiseidler M, Wenzel D, Hesse M, Fürst DO, Saftig P, Saint R, Fleischmann BK, Hoch M, Höhfeld J (2010). "Chaperone-assisted selective autophagy is essential for muscle maintenance". Curr Biol. 20 (2): 143–8. doi:10.1016/j.cub.2009.11.022. PMID 20060297. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ a b c Ulbricht A, Eppler FJ, Tapia VE, van der Ven PF, Hampe N, Hersch N, Vakeel P, Stadel D, Haas A, Saftig P, Behrends C, Fürst DO, Volkmer R, Hoffmann B, Kolanus W, Höhfeld J. (2013). "Cellular Mechanotransduction Relies on Tension-Induced and Chaperone-Assisted Autophagy". Curr Biol. 23 (5): 430–5. doi:10.1016/j.cub.2013.01.064. PMID 23434281. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  6. ^ Gamerdinger M, Hajieva P, Kaya AM, Wolfrum U, Hartl FU, Behl C. 2009" EMBO J 28(7) 889-901. Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3
  7. ^ Physorg:Old Cells Work Differently
  8. ^ Norton, N (2011 Mar 11). "Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy". American Journal of Human Genetics. 88 (3): 273–82. doi:10.1016/j.ajhg.2011.01.016. PMC 3059419. PMID 21353195. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  9. ^ Villard, E (April 1, 2011). "A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy". 32 (9): 1065–76. doi:10.1093/eurheartj/ehr105. PMID 21459883. {{cite journal}}: Cite journal requires |journal= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  10. ^ a b Doong, H (2000). "CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70". Oncogene. 19 (38). ENGLAND: 4385–95. doi:10.1038/sj.onc.1203797. ISSN 0950-9232. PMID 10980614. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  11. ^ Antoku, K (2001). "Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein". Biochem. Biophys. Res. Commun. 286 (5). United States: 1003–10. doi:10.1006/bbrc.2001.5512. ISSN 0006-291X. PMID 11527400. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  12. ^ Gamerdinger et al., 2011 BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins.

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