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CITED Proteins in Cardiac Development and Lifelong Heart Function
José Bragança1,2,3, Rute Luísa Cabrita Pinto1,2, Igor Ventura1
1Faculty of Medicine and Biomedical Sciences (FMCB), Campus Gambelas, University of Algarve, 8005-139 Faro, Portugal.
Insights
CITED proteins are crucial for vertebrate development, especially heart formation. CITED2 deficiency causes congenital heart disease, but CITED2 and CITED4 may offer new therapeutic avenues for heart conditions.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cardiology
Background:
- CITED proteins are transcriptional modulators vital for vertebrate development.
- They interact with transcription factors and co-activators, featuring a conserved domain binding CBP/p300.
- CITED gene expression is prominent in embryonic cardiac development.
Purpose of the Study:
- To analyze CITED proteins, their interactors, and target genes in cardiogenesis and heart disease.
- To explore the role of CITED2 and CITED4 in cardiac development and disease.
- To highlight potential therapeutic applications of CITED proteins in cardiovascular conditions.
Main Methods:
- Literature review and analysis of existing research on CITED proteins.
- Examination of gene expression patterns during embryogenesis.
- Review of studies linking CITED protein function to congenital heart disease and cardiac adaptation.
Main Results:
- CITED2 loss-of-function is strongly linked to congenital heart malformations in animal models and humans.
- CITED2 and CITED4 are implicated in regulating physiological adaptations and stress responses in the heart.
- Specific CITED-target genes relevant to cardiogenesis and heart disease were identified.
Conclusions:
- CITED2 plays a critical role in heart development, and its dysfunction leads to congenital heart disease (CHD).
- CITED2 and CITED4 show potential as therapeutic targets for mitigating CHD and preserving cardiac function.
- Further research into CITED proteins may yield novel strategies for treating heart disease.
Abstract:
The CITED proteins function as transcriptional modulators that are essential for vertebrate development. These proteins interact with numerous partners, notably transcription factors and co-activators. The hallmark of the CITED family is their conserved carboxy-terminal domain, which interacts strongly with the CBP/p300 co-activators. The expression of CITED genes is detected early during embryogenesis within embryonic and foetal regions critical for cardiac morphogenesis, among other developmental processes. Notably, CITED2 loss of function is strongly associated with congenital heart malformations in mice and zebrafish embryos, as well as congenital heart disease (CHD) in humans, whereas other CITED family members are not critical for cardiogenesis. Emerging evidence implicates CITED2 and CITED4 in regulating heart physiological adaptations and protective responses to pathological stress. This review provides a detailed analysis of CITED proteins and their interactors, focusing on CITED-target genes relevant for cardiogenesis and heart disease. We also highlight recent findings indicating that CITED2 and CITED4 may be instrumental for the development of novel therapeutic strategies to mitigate CHD and preserve adult cardiac function.
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