CD44a functions as a regulator of p53 signaling, apoptosis and autophagy in the antibacterial immune response
- Cao, L., Fang, H., Yan, D., Wu, X.M., Zhang, J., Chang, M.X.
- Communications biology 5: 889 (Journal)
- Registered Authors
- Cao, Lu, Chang, Mingxian, Wu, Xiaoman
- MeSH Terms
- Anti-Bacterial Agents/metabolism
- Anti-Bacterial Agents/pharmacology
- Tumor Suppressor Protein p53*/genetics
- Tumor Suppressor Protein p53*/metabolism
- 36042265 Full text @ Commun Biol
Cao, L., Fang, H., Yan, D., Wu, X.M., Zhang, J., Chang, M.X. (2022) CD44a functions as a regulator of p53 signaling, apoptosis and autophagy in the antibacterial immune response. Communications biology. 5:889.
The cell adhesion molecule CD44 has been implicated in diverse biological functions including the pathological responses to infections and inflammatory diseases. The variable forms of CD44 contribute to functional variations, which are not yet defined in teleost. Here, we show that zebrafish CD44a plays a protective role in the host defense against Edwardsiella piscicida infection. Zebrafish CD44a deficiency inhibits cell growth and proliferation, impairs cell growth and death pathways, and regulates the expression levels of many genes involved in p53 signaling, apoptosis and autophagy. In addition, CD44a gene disruption in zebrafish leads to inhibition of apoptosis and induction of autophagy, with the increased susceptibility to E. piscicida infection. Furthermore, we show that zebrafish CD44a variants including CD44a_tv1 and CD44a_tv2 promote the translocation of p53 from the nucleus to the cytoplasm and interact with p53 in the cytoplasm. Mechanistically, zebrafish CD44a_tv1 mediates the beneficial effect for larvae survival infected with E. piscicida is depending on the CASP8-mediated apoptosis. However, the antibacterial effect of zebrafish CD44a_tv2 depends on the cytoplasmic p53-mediated inhibition of autophagy. Collectively, our results identify that different mechanisms regulate CD44a variants-mediated antibacterial responses.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes