E2F transcription factor 1 (E2F1) promotes the transforming growth factor TGF-β1 induced human cardiac fibroblasts differentiation through promoting the transcription of CCNE2 gene

Liao, Rongheng; Xie, Bo; Cui, Jun; Qi, Zhengjian; Xue, Song; Wang, Yong-Yi

doi:10.1080/21655979.2021.1972194

Cited by 11 publications

(2 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, E2F1 can upregulate VEGF and PIGF through both p53-dependent and -independent pathways, facilitating neovascularization in the myocardial infarction area (Wu et al, 2014). E2F1 also contributes to the differentiation of human cardiac fibroblasts and promotes Tgfβ1-induced cell differentiation, leading to myocardial fibrosis by directly targeting CCNE2 (Liao et al, 2021). Importantly, E2F1 has strong correlation with Setd7 predicted by HitPredict database.…”

Section: Discussionmentioning

confidence: 94%

Deletion of Setd7 protects against cardiac hypertrophy via inhibiting lipid oxidation

Su,

Wang,

Zhang

et al. 2024

Preprint

View full text Add to dashboard Cite

Setd7, a catalytic enzyme responsible for histone H3K4 methylation, is implicated in various cardiac diseases. However, the role of Setd7 in pathological cardiac hypertrophy remains unclear. In this study, we observed that Setd7 is significantly elevated in pathological hypertrophy stimuli cardiomyocytes and mouse failing hearts. Subsequently, we found that mice lacking Setd7 remarkably preserved cardiac function after transverse aortic constriction, as demonstrated by improving myocardial hypertrophy and fibrosis, whereas Setd7 overexpression in cardiomyocytes deteriorated hypertrophy phenotype. Further in vitro analyses revealed that Setd7 mediated-E2F1 activation induces E3 ubiquitin protein ligases WWP2 expression to catalyze the lipid-peroxide-reducing enzyme GPx4 ubiquitination degradation, ultimately causing widespread lipid peroxidation and boosting pathological cardiac hypertrophy. Remarkably, loss of activity of GPx4 blunted the Setd7 knockdown exerts antihypertrophic effect in pathological cardiomyocytes hypertrophy, further confirming an important role of lipid peroxidation in Setd7-mediated failing hearts. In summary, the role of Setd7 in pressure overload-induced cardiac hypertrophy is regulated by the Setd7-E2F1-WWP2-GPx4 signaling pathway, suggesting that targeting Setd7 is a promising therapeutic strategy to attenuate pathological cardiac hypertrophy and heart failure.

show abstract

Section: Discussionmentioning

confidence: 94%

Deletion of Setd7 protects against cardiac hypertrophy via inhibiting lipid oxidation

Su,

Wang,

Zhang

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Cyclin E2 (CCNE2), a known E2F1 target (14,15), was found to be the gene most strongly affected by the absence of M117 in MCMV-infected RPE-1 cells (Fig 2C). CCNE proteins are involved in cell cycle regulation as well as in DNA replication (16), but an antiviral function has not been described for these proteins.…”

Section: Ccne2 Is Not An MCMV Restriction Factormentioning

confidence: 99%

E2F3-dependent activation of FAM111B restricts mouse cytomegalovirus replication in primate cells

Ostermann,

Luoto,

Clausen

et al. 2024

Preprint

View full text Add to dashboard Cite

Cytomegaloviruses are highly species-specific as they replicate only in cells of their own or a closely related species. For instance, human cytomegalovirus cannot replicate in rodent cells, and mouse cytomegalovirus (MCMV) cannot replicate in human and monkey cells. However, the mechanisms underlying the host species restriction remain poorly understood. We have previously shown that passaging MCMV in human retinal pigment epithelial cells allows the virus to replicate to high titers in these cells due to the accumulation of adaptive mutations, such as loss-of-function mutations in the viral M117 gene. The M117 protein interacts with E2F transcription factors and activates E2F-dependent transcription. Here we show that activation of E2F3 is primarily responsible for MCMV’s inability to replicate in human cells. By transcriptome analysis, we identified two E2F3-induced serine proteases, FAM111A and FAM111B, as potential host restriction factors. By using shRNA-mediated gene knockdown and CRISPR/Cas9-mediated gene knockout, we demonstrated that FAM111B, but not its paralog FAM111A, suppresses MCMV replication in human and rhesus macaque cells. By immunofluorescence, we detected FAM111B predominantly in the nucleus of infected cells with enrichment in viral replication compartments, suggesting that it might play a role during viral replication. The fact that the FAM111B gene is conserved in primates but absent in rodents suggests that MCMV has not evolved to evade or counteract this restriction factor, which is not present in its natural host.ImportanceViruses must counteract host cell defenses to facilitate viral replication. Viruses with a narrow host range, such as the cytomegaloviruses, are unable to counteract cellular defenses in cells of a foreign species. However, little is known about the cellular host range factors restricting cytomegalovirus replication. Here we show that MCMV induces the expression of the FAM111 proteases and that FAM111B, but not FAM111A that has previously been shown to restrict the replication of polyomavirus and orthopoxvirus host range mutants, acts as a cellular factor suppressing MCMV replication in human and rhesus monkey cells. The identification of FAM111B as a host range factor should provide new insight into the physiological functions of this poorly characterized protein.

show abstract

The E2F family: a ray of dawn in cardiomyopathy

Wei,

Gao,

et al. 2024

Mol Cell Biochem

View full text Add to dashboard Cite

E2F transcription factor 1 (E2F1) promotes the transforming growth factor TGF-β1 induced human cardiac fibroblasts differentiation through promoting the transcription of CCNE2 gene

Abstract: E2F transcription factor 1 (E2F1) promotes the transforming growth factor TGF-β1 induced human cardiac fibroblasts differentiation through promoting the transcription of CCNE2 gene,

Cited by 11 publications

References 39 publications

Deletion of Setd7 protects against cardiac hypertrophy via inhibiting lipid oxidation

Deletion of Setd7 protects against cardiac hypertrophy via inhibiting lipid oxidation

E2F3-dependent activation of FAM111B restricts mouse cytomegalovirus replication in primate cells

The E2F family: a ray of dawn in cardiomyopathy

Contact Info

Product

Resources

About