The Zebrafish Antiapoptotic Protein BIRC2 Promotes Edwardsiella piscicida Infection by Inhibiting Caspases and Accumulating p53 in a p53 Transcription-Dependent and -Independent Manner
IAPs (inhibitors of apoptosis) are endogenous caspase inhibitors with multiple biological activities. In the present study, we show functional characteristics of antiapoptotic protein BIRC2 (cIAP1) in response to Edwardsiella piscicida infection. Overexpression of BIRC2 in zebrafish larvae promoted...
Guardado en:
| Autores principales: | , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/d75e20c2ee5040f0818dfa8116b2fa52 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:d75e20c2ee5040f0818dfa8116b2fa52 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:d75e20c2ee5040f0818dfa8116b2fa522021-11-30T14:34:16ZThe Zebrafish Antiapoptotic Protein BIRC2 Promotes Edwardsiella piscicida Infection by Inhibiting Caspases and Accumulating p53 in a p53 Transcription-Dependent and -Independent Manner1664-322410.3389/fimmu.2021.781680https://doaj.org/article/d75e20c2ee5040f0818dfa8116b2fa522021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.781680/fullhttps://doaj.org/toc/1664-3224IAPs (inhibitors of apoptosis) are endogenous caspase inhibitors with multiple biological activities. In the present study, we show functional characteristics of antiapoptotic protein BIRC2 (cIAP1) in response to Edwardsiella piscicida infection. Overexpression of BIRC2 in zebrafish larvae promoted the proliferation of E. piscicida, leading to a decreased larvae survival. The expression levels of caspases including casp3, casp8, and casp9 were significantly inhibited by BIRC2 overexpression in the case of E. piscicida infection. Treatment of zebrafish larvae microinjected with BIRC2 with the caspase activator PAC-1 completely blocked the negative regulation of BIRC2 on the E. piscicida infection, with the reduced inhibition on the casp3 and without inhibition on casp8 and casp9. In contrast to the regulation of BIRC2 on the caspases, BIRC2 overexpression significantly induced the expression of p53, especially at 24 hpi. In addition to the cytoplasmic p53 expression, BIRC2 overexpression also induced the expression of the nuclear p53 protein. Further analysis demonstrated that BIRC2 could interact and colocalize with p53 in the cytoplasm. The numbers of E. piscicida in larvae overexpressed with BIRC2 and treated with pifithrin-μ (an inhibitor of mitochondrial p53) or pifithrin-α (an inhibitor of p53 transactivation) were lower than those of larvae without pifithrin-μ or pifithrin-α treatment. Critically, the p53 inactivators pifithrin-μ and pifithrin-α had no significant effect on larval survival, but completely rescued larval survival for zebrafish microinjected with BIRC2 in the case of E. piscicida infection. Collectively, the present study suggest that piscine BIRC2 is a negative regulator for antibacterial immune response in response to the E. piscicida infection via inhibiting caspases, and accumulating p53 in a p53 transcription-dependent and -independent manner.Lu CaoLu CaoDong YanDong YanJun XiaoHao FengMing Xian ChangMing Xian ChangMing Xian ChangFrontiers Media S.A.articleantiapoptotic protein BIRC2caspasesp53negative regulationEdwardsiella piscicida infectionImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
antiapoptotic protein BIRC2 caspases p53 negative regulation Edwardsiella piscicida infection Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
antiapoptotic protein BIRC2 caspases p53 negative regulation Edwardsiella piscicida infection Immunologic diseases. Allergy RC581-607 Lu Cao Lu Cao Dong Yan Dong Yan Jun Xiao Hao Feng Ming Xian Chang Ming Xian Chang Ming Xian Chang The Zebrafish Antiapoptotic Protein BIRC2 Promotes Edwardsiella piscicida Infection by Inhibiting Caspases and Accumulating p53 in a p53 Transcription-Dependent and -Independent Manner |
| description |
IAPs (inhibitors of apoptosis) are endogenous caspase inhibitors with multiple biological activities. In the present study, we show functional characteristics of antiapoptotic protein BIRC2 (cIAP1) in response to Edwardsiella piscicida infection. Overexpression of BIRC2 in zebrafish larvae promoted the proliferation of E. piscicida, leading to a decreased larvae survival. The expression levels of caspases including casp3, casp8, and casp9 were significantly inhibited by BIRC2 overexpression in the case of E. piscicida infection. Treatment of zebrafish larvae microinjected with BIRC2 with the caspase activator PAC-1 completely blocked the negative regulation of BIRC2 on the E. piscicida infection, with the reduced inhibition on the casp3 and without inhibition on casp8 and casp9. In contrast to the regulation of BIRC2 on the caspases, BIRC2 overexpression significantly induced the expression of p53, especially at 24 hpi. In addition to the cytoplasmic p53 expression, BIRC2 overexpression also induced the expression of the nuclear p53 protein. Further analysis demonstrated that BIRC2 could interact and colocalize with p53 in the cytoplasm. The numbers of E. piscicida in larvae overexpressed with BIRC2 and treated with pifithrin-μ (an inhibitor of mitochondrial p53) or pifithrin-α (an inhibitor of p53 transactivation) were lower than those of larvae without pifithrin-μ or pifithrin-α treatment. Critically, the p53 inactivators pifithrin-μ and pifithrin-α had no significant effect on larval survival, but completely rescued larval survival for zebrafish microinjected with BIRC2 in the case of E. piscicida infection. Collectively, the present study suggest that piscine BIRC2 is a negative regulator for antibacterial immune response in response to the E. piscicida infection via inhibiting caspases, and accumulating p53 in a p53 transcription-dependent and -independent manner. |
| format |
article |
| author |
Lu Cao Lu Cao Dong Yan Dong Yan Jun Xiao Hao Feng Ming Xian Chang Ming Xian Chang Ming Xian Chang |
| author_facet |
Lu Cao Lu Cao Dong Yan Dong Yan Jun Xiao Hao Feng Ming Xian Chang Ming Xian Chang Ming Xian Chang |
| author_sort |
Lu Cao |
| title |
The Zebrafish Antiapoptotic Protein BIRC2 Promotes Edwardsiella piscicida Infection by Inhibiting Caspases and Accumulating p53 in a p53 Transcription-Dependent and -Independent Manner |
| title_short |
The Zebrafish Antiapoptotic Protein BIRC2 Promotes Edwardsiella piscicida Infection by Inhibiting Caspases and Accumulating p53 in a p53 Transcription-Dependent and -Independent Manner |
| title_full |
The Zebrafish Antiapoptotic Protein BIRC2 Promotes Edwardsiella piscicida Infection by Inhibiting Caspases and Accumulating p53 in a p53 Transcription-Dependent and -Independent Manner |
| title_fullStr |
The Zebrafish Antiapoptotic Protein BIRC2 Promotes Edwardsiella piscicida Infection by Inhibiting Caspases and Accumulating p53 in a p53 Transcription-Dependent and -Independent Manner |
| title_full_unstemmed |
The Zebrafish Antiapoptotic Protein BIRC2 Promotes Edwardsiella piscicida Infection by Inhibiting Caspases and Accumulating p53 in a p53 Transcription-Dependent and -Independent Manner |
| title_sort |
zebrafish antiapoptotic protein birc2 promotes edwardsiella piscicida infection by inhibiting caspases and accumulating p53 in a p53 transcription-dependent and -independent manner |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/d75e20c2ee5040f0818dfa8116b2fa52 |
| work_keys_str_mv |
AT lucao thezebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT lucao thezebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT dongyan thezebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT dongyan thezebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT junxiao thezebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT haofeng thezebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT mingxianchang thezebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT mingxianchang thezebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT mingxianchang thezebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT lucao zebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT lucao zebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT dongyan zebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT dongyan zebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT junxiao zebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT haofeng zebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT mingxianchang zebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT mingxianchang zebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner AT mingxianchang zebrafishantiapoptoticproteinbirc2promotesedwardsiellapiscicidainfectionbyinhibitingcaspasesandaccumulatingp53inap53transcriptiondependentandindependentmanner |
| _version_ |
1718406533396561920 |