Anamorsin, a Novel Caspase-3 Substrate in Neurodegeneration
DC Field | Value | Language |
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dc.contributor.author | Yun, Nuri | - |
dc.contributor.author | Lee, Young Mook | - |
dc.contributor.author | Kim, Chiho | - |
dc.contributor.author | Shibayama, Hirohiko | - |
dc.contributor.author | Tanimura, Akira | - |
dc.contributor.author | Hamanaka, Yuri | - |
dc.contributor.author | Kanakura, Yuzuru | - |
dc.contributor.author | Park, Il-Seon | - |
dc.contributor.author | Jo, Areum | - |
dc.contributor.author | Shin, Joo-Ho | - |
dc.contributor.author | Ju, Chung | - |
dc.contributor.author | Kim, Won-Ki | - |
dc.contributor.author | Oh, Young J. | - |
dc.date.accessioned | 2021-09-05T06:11:15Z | - |
dc.date.available | 2021-09-05T06:11:15Z | - |
dc.date.created | 2021-06-15 | - |
dc.date.issued | 2014-08-08 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/97702 | - |
dc.description.abstract | Activated caspases play a central role in the execution of apoptosis by cleaving endogenous substrates. Here, we developed a high throughput screening method to identify novel substrates for caspase-3 in a neuronal cell line. Critical steps in our strategy consist of two-dimensional electrophoresis-based protein separation and in vitro caspase-3 incubation of immobilized proteins to sort out direct substrates. Among 46 putative substrates identified in MN9D neuronal cells, we further evaluated whether caspase-3-mediated cleavage of anamorsin, a recently recognized cell death-defying factor in hematopoiesis, is a general feature of apoptosis. In vitro and cell-based cleavage assays indicated that anamorsin was specifically cleaved by caspase-3 but not by other caspases, generating 25- and 10-kDa fragments. Thus, in apoptosis of neuronal and non-neuronal cells induced by various stimuli including staurosporine, etoposide, or 6-hydroxydopamine, the cleavage of anamorsin was found to be blocked in the presence of caspase inhibitor. Among four tetrapeptide consensus DXXD motifs existing in anamorsin, we mapped a specific cleavage site for caspase-3 at DSVD209 down arrow L. Intriguingly, the 25-kDa cleaved fragment of anamorsin was also detected in post-mortem brains of Alzheimer and Parkinson disease patients. Although the RNA interference-mediated knockdown of anamorsin rendered neuronal cells more vulnerable to staurosporine treatment, reintroduction of full-length anamorsin into an anamorsin knock-out stromal cell line made cells resistant to staurosporine-induced caspase activation, indicating the antiapoptotic function of anamorsin. Taken together, our approach seems to be effective to identify novel substrates for caspases and has the potential to provide meaningful insights into newly identified substrates involved in neurodegenerative processes. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | - |
dc.subject | SULFUR PROTEIN BIOGENESIS | - |
dc.subject | FAS-INDUCED APOPTOSIS | - |
dc.subject | DOPAMINERGIC-NEURONS | - |
dc.subject | OXIDATIVE STRESS | - |
dc.subject | CELL-DEATH | - |
dc.subject | MULTIDRUG-RESISTANCE | - |
dc.subject | PARKINSONS-DISEASE | - |
dc.subject | ALZHEIMERS-DISEASE | - |
dc.subject | CANCER CELLS | - |
dc.subject | ROCK-I | - |
dc.title | Anamorsin, a Novel Caspase-3 Substrate in Neurodegeneration | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Won-Ki | - |
dc.identifier.doi | 10.1074/jbc.M114.552679 | - |
dc.identifier.scopusid | 2-s2.0-84905851425 | - |
dc.identifier.wosid | 000340593500033 | - |
dc.identifier.bibliographicCitation | JOURNAL OF BIOLOGICAL CHEMISTRY, v.289, no.32, pp.22183 - 22195 | - |
dc.relation.isPartOf | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.citation.title | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.citation.volume | 289 | - |
dc.citation.number | 32 | - |
dc.citation.startPage | 22183 | - |
dc.citation.endPage | 22195 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.subject.keywordPlus | SULFUR PROTEIN BIOGENESIS | - |
dc.subject.keywordPlus | FAS-INDUCED APOPTOSIS | - |
dc.subject.keywordPlus | DOPAMINERGIC-NEURONS | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | CELL-DEATH | - |
dc.subject.keywordPlus | MULTIDRUG-RESISTANCE | - |
dc.subject.keywordPlus | PARKINSONS-DISEASE | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | CANCER CELLS | - |
dc.subject.keywordPlus | ROCK-I | - |
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