RGD Reference Report - FAT10 attenuates hypoxia-induced cardiomyocyte apoptosis by stabilizing caveolin-3. - Rat Genome Database

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FAT10 attenuates hypoxia-induced cardiomyocyte apoptosis by stabilizing caveolin-3.

Authors: Zhou, Qiongqiong  Peng, Xiaogang  Liu, Xiao  Chen, Leifeng  Xiong, Qinmei  Shen, Yang  Xie, Jinyan  Xu, Zhenyan  Huang, Lin  Hu, Jinzhu  Wan, Rong  Hong, Kui 
Citation: Zhou Q, etal., J Mol Cell Cardiol. 2018 Mar;116:115-124. doi: 10.1016/j.yjmcc.2018.02.008. Epub 2018 Feb 10.
RGD ID: 126925221
Pubmed: PMID:29438664   (View Abstract at PubMed)
DOI: DOI:10.1016/j.yjmcc.2018.02.008   (Journal Full-text)

FAT10, a member of the ubiquitin-like-modifier family of proteins, plays a cardioprotective role in response to hypoxic/ischemic injury. Caveolin-3 (Cav-3), a muscle-specific caveolin family member, is involved in cardiomyocyte apoptosis. However, the link between FAT10 and Cav-3 in ischemic cardiomyocytes is unclear. In the present study, we found that both FAT10 and Cav-3 were upregulated in ischemic myocardial tissues and in hypoxic cardiomyocytes. Furthermore, our results demonstrated that FAT10 inhibits hypoxia-induced cardiomyocyte apoptosis by increasing Cav-3 expression. Importantly, following myocardial infarction, knockout of FAT10 aggravated cardiac dysfunction and increased cardiomyocyte apoptosis by reducing Cav-3 expression. Additionally, Cav-3 was degraded by the ubiquitin-proteasome system (UPS) in cardiomyocytes. Mechanistically, we found that FAT10 stabilizes Cav-3 expression by inhibiting ubiquitination-mediated degradation in cardiomyocytes. Together, these findings revealed a novel role of FAT10 in protection against ischemia-induced injury via stabilization of Cav-3, providing evidence that the FAT10/Cav-3 axis may be a potential therapeutic target for patients with ischemic heart conditions.

Disease Annotations    
myocardial infarction  (IEP,IMP,ISO)

Gene Ontology Annotations    

Biological Process

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Cav3  (caveolin 3)
Ubd  (ubiquitin D)
Ubdem1  (ubiquitin D; CRISPR/Cas9 induced mutant1)

Genes (Mus musculus)
Cav3  (caveolin 3)
Ubd  (ubiquitin D)

Genes (Homo sapiens)
CAV3  (caveolin 3)
UBD  (ubiquitin D)

SD-Ubdem1  (NA)

Additional Information