2016 Fiscal Year Final Research Report
Regulatory mechanism of intracellular localization of PAR in neuronal cell death
| Project/Area Number |
15K18871
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biological pharmacy
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| Research Institution | Doshisha Women's College of Liberal Arts |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | Parthanatos / DNA damage / cell death / PARP1 / caspase / apoptosis |
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| Outline of Final Research Achievements |
Parthanatos is a programed cell death resulting from a PARP1-dependent manner. Upon sensing DNA damage, activated PARP1 generates PAR polymers, which acts signaling molecules to transduce nuclear information to the cytoplasm and mitochondria. After translocating to the cytoplasm, PAR polymers bind apoptosis-inducing factor (AIF) via their PAR-binding motif. AIF is cleaved and released from mitochondrial membrane. After translocating to the nucleus, AIF induces DNA fragmentation. In the pathway, PAR translocation to the cytoplasm appears a critical step, but its mechanism is unknown.
We found that PARP1 was cleaved by caspase 3, generating 89-kDa and 24-kDa PARP1 fragments. 89-kDa PARP1 fragment was automodifed by PAR and translocated to the cytoplasm with attaching PAR polymers. In the cytoplasm, the automodfed 89-kDa PARP1 fragment was associate with AIF. Thus, PARP1 fragmentation is an important step to carry PAR from the nucleus to the cytoplasm to induce parthanatos.
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| Free Research Field |
分子生物学
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