SUMMARY:
The IPV motif in protein aggregation by analyzing a potential association between DCM and CMT2.
TITLE:
The role of BAG3 in dilated cardiomyopathy and its association with Charcot-Marie-Tooth disease type 2
DESCRIPTION:
Bcl2-associated athanogene 3 (BAG3) is a multifunctional cochaperone responsible for protein quality control within cells. BAG3 interacts with chaperones HSPB8 and Hsp70 to transport misfolded proteins to the Microtubule Organizing Center (MTOC) and degrade them in autophagosomes in a process known as Chaperone Assisted Selective Autophagy (CASA). Mutations in the second conserved IPV motif of BAG3 are known to cause Dilated Cardiomyopathy (DCM) by inhibiting adequate removal of non-native…
CONTENT:
Acta Myol. 2022 Jun 30;41(2):59-75. doi: 10.36185/2532-1900-071. eCollection 2022 Jun.
ABSTRACT
Bcl2-associated athanogene 3 (BAG3) is a multifunctional cochaperone responsible for protein quality control within cells. BAG3 interacts with chaperones HSPB8 and Hsp70 to transport misfolded proteins to the Microtubule Organizing Center (MTOC) and degrade them in autophagosomes in a process known as Chaperone Assisted Selective Autophagy (CASA). Mutations in the second conserved IPV motif of BAG3 are known to cause Dilated Cardiomyopathy (DCM) by inhibiting adequate removal of non-native proteins. The proline 209 to leucine (P209L) BAG3 mutant in particular causes the aggregation of BAG3 and misfolded proteins as well as the sequestration of essential chaperones. The exact mechanisms of protein aggregation in DCM are unknown. However, the similar presence of insoluble protein aggregates in Charcot-Marie-Tooth disease type 2 (CMT2) induced by the proline 182 to leucine (P182L) HSPB1 mutant points to a possible avenue for future research: IPV motif. In this review, we summarize the molecular mechanisms of CASA and the currently known pathological effects of mutated BAG3 in DCM. Additionally, we will provide insight on the importance of the IPV motif in protein aggregation by analyzing a potential association between DCM and CMT2.
PMID:35832504 | PMC:PMC9237749 | DOI:10.36185/2532-1900-071
SOURCE:
Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology
TAGS:
DCM CMT2
CATEGORY:
Research
SUBCATEGORY:
n/a
DATE – PUBLISHED:
2022-06-28T08:09:57Z
DATE – DOI: 2022-06-28T08:09:57Z
DATE – PUBMED: 2022 Jun 30
DATE OUTPUT MATCHED: True
DATE – ADDED:
Thu, 14 Jul 2022 06:00:00 -0400
DATE – RETRIEVED:
07/14/22 07:35AM
2022-07-14T07:35:38-04:00
FEATURED IMAGE:
Media Uploaded (image/png)
IDENTIFIER:
pmid:35832504,pmc:PMC9237749,doi:10.36185/2532-1900-071
PUBMED ID:
pubmed:35832504
DOI:
10.36185/2532-1900-071
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/35832504/
LINK – DOI:
https://doi.org/10.36185/2532-1900-071
LINK – PUBLISHER:
https://www.actamyologica.it/article/the-role-of-bag3-in-dilated-cardiomyopathy-and-its-association-with-charcot-marie-tooth-disease-type-2/
REFERENCES:
CMT Treatment Report, Urgent Research, 2022-07-14T07:35:38-04:00, https://www.cmttreatmentreport.com.
