The proapoptotic activity of C-terminal domain of apoptosis-inducing factor (AIF) is separated from its N-terminal
Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that mediates both NADH-oxidizing and caspase-independent apoptosis. Further, the proapoptotic activity of AIF is located in the C-terminus of AIF, although the precise minimum sequence responsible for apoptosis induction remains to be...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , |
|---|---|
| Lenguaje: | English |
| Publicado: |
Sociedad de Biología de Chile
2009
|
| Materias: | |
| Acceso en línea: | http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602009000200014 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:scielo:S0716-97602009000200014 |
|---|---|
| record_format |
dspace |
| spelling |
oai:scielo:S0716-976020090002000142009-10-09The proapoptotic activity of C-terminal domain of apoptosis-inducing factor (AIF) is separated from its N-terminalZHANG,YONGHAN,TAOZHU,QINGZHANG,WEIBAO,WEIFU,HAI-JINGYANG,JIEHUANG,XIAO-JUNWEI,JUN-XIAMENG,YAN-LINGZHAO,JINGCAO,YUN-XINJIA,LIN-TAOYANG,AN-GANG apoptosis inducing factor (AIF) apoptosis cytochrome c mitochondria HER2 Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that mediates both NADH-oxidizing and caspase-independent apoptosis. Further, the proapoptotic activity of AIF is located in the C-terminus of AIF, although the precise minimum sequence responsible for apoptosis induction remains to be investigated. In the present study, we generated two truncated AIFs, AIFΔ1-480-FLAG, which is a FLAG-tagged C-terminal peptide comprising amino acids from 481 to 613, and AIF360-480 containing amino acids from 360 to 480 of AIF. We used confocal microscopy to demonstrate that both the truncated proteins are expressed and located in the cytoplasm of transfected cells. AIFΔ1-480 but not AIF360-480 induces apoptosis in transfected cells. We also found that the expression of AIFΔ1-480 could initiate the release of cytochrome c from the mitochondria. The suppression of caspase-9 via siRNA blocked the proapoptotic activity of AIFΔ1-480. Therefore, AIFΔ 1-480 is sufficient for inducing caspase-9-dependent apoptotic signaling, probably by promoting the release of cytochrome c. At last, we generated a chimeric immuno-AIFΔ 1-480 protein, which comprised an HER2 antibody, a Pseudomonas exotoxin A translocation domain and AIFΔ 1-480. Human Jurkat cells transfected with the immuno-AIFΔl-480 gene could express and secrete the chimeric protein, which selectively recognize and kill HER2-overexpressing tumor cells. Our study demonstrates the feasibility of the immuno-AIFΔl-480 gene as a novel approach to treating HER2-overexpressing cancers.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.42 n.2 20092009-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602009000200014en10.4067/S0716-97602009000200014 |
| institution |
Scielo Chile |
| collection |
Scielo Chile |
| language |
English |
| topic |
apoptosis inducing factor (AIF) apoptosis cytochrome c mitochondria HER2 |
| spellingShingle |
apoptosis inducing factor (AIF) apoptosis cytochrome c mitochondria HER2 ZHANG,YONG HAN,TAO ZHU,QING ZHANG,WEI BAO,WEI FU,HAI-JING YANG,JIE HUANG,XIAO-JUN WEI,JUN-XIA MENG,YAN-LING ZHAO,JING CAO,YUN-XIN JIA,LIN-TAO YANG,AN-GANG The proapoptotic activity of C-terminal domain of apoptosis-inducing factor (AIF) is separated from its N-terminal |
| description |
Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that mediates both NADH-oxidizing and caspase-independent apoptosis. Further, the proapoptotic activity of AIF is located in the C-terminus of AIF, although the precise minimum sequence responsible for apoptosis induction remains to be investigated. In the present study, we generated two truncated AIFs, AIFΔ1-480-FLAG, which is a FLAG-tagged C-terminal peptide comprising amino acids from 481 to 613, and AIF360-480 containing amino acids from 360 to 480 of AIF. We used confocal microscopy to demonstrate that both the truncated proteins are expressed and located in the cytoplasm of transfected cells. AIFΔ1-480 but not AIF360-480 induces apoptosis in transfected cells. We also found that the expression of AIFΔ1-480 could initiate the release of cytochrome c from the mitochondria. The suppression of caspase-9 via siRNA blocked the proapoptotic activity of AIFΔ1-480. Therefore, AIFΔ 1-480 is sufficient for inducing caspase-9-dependent apoptotic signaling, probably by promoting the release of cytochrome c. At last, we generated a chimeric immuno-AIFΔ 1-480 protein, which comprised an HER2 antibody, a Pseudomonas exotoxin A translocation domain and AIFΔ 1-480. Human Jurkat cells transfected with the immuno-AIFΔl-480 gene could express and secrete the chimeric protein, which selectively recognize and kill HER2-overexpressing tumor cells. Our study demonstrates the feasibility of the immuno-AIFΔl-480 gene as a novel approach to treating HER2-overexpressing cancers. |
| author |
ZHANG,YONG HAN,TAO ZHU,QING ZHANG,WEI BAO,WEI FU,HAI-JING YANG,JIE HUANG,XIAO-JUN WEI,JUN-XIA MENG,YAN-LING ZHAO,JING CAO,YUN-XIN JIA,LIN-TAO YANG,AN-GANG |
| author_facet |
ZHANG,YONG HAN,TAO ZHU,QING ZHANG,WEI BAO,WEI FU,HAI-JING YANG,JIE HUANG,XIAO-JUN WEI,JUN-XIA MENG,YAN-LING ZHAO,JING CAO,YUN-XIN JIA,LIN-TAO YANG,AN-GANG |
| author_sort |
ZHANG,YONG |
| title |
The proapoptotic activity of C-terminal domain of apoptosis-inducing factor (AIF) is separated from its N-terminal |
| title_short |
The proapoptotic activity of C-terminal domain of apoptosis-inducing factor (AIF) is separated from its N-terminal |
| title_full |
The proapoptotic activity of C-terminal domain of apoptosis-inducing factor (AIF) is separated from its N-terminal |
| title_fullStr |
The proapoptotic activity of C-terminal domain of apoptosis-inducing factor (AIF) is separated from its N-terminal |
| title_full_unstemmed |
The proapoptotic activity of C-terminal domain of apoptosis-inducing factor (AIF) is separated from its N-terminal |
| title_sort |
proapoptotic activity of c-terminal domain of apoptosis-inducing factor (aif) is separated from its n-terminal |
| publisher |
Sociedad de Biología de Chile |
| publishDate |
2009 |
| url |
http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602009000200014 |
| work_keys_str_mv |
AT zhangyong theproapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT hantao theproapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT zhuqing theproapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT zhangwei theproapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT baowei theproapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT fuhaijing theproapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT yangjie theproapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT huangxiaojun theproapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT weijunxia theproapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT mengyanling theproapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT zhaojing theproapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT caoyunxin theproapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT jialintao theproapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT yangangang theproapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT zhangyong proapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT hantao proapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT zhuqing proapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT zhangwei proapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT baowei proapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT fuhaijing proapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT yangjie proapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT huangxiaojun proapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT weijunxia proapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT mengyanling proapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT zhaojing proapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT caoyunxin proapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT jialintao proapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal AT yangangang proapoptoticactivityofcterminaldomainofapoptosisinducingfactoraifisseparatedfromitsnterminal |
| _version_ |
1718441447958511616 |