Source:http://linkedlifedata.com/resource/pubmed/id/17670986
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
31
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pubmed:dateCreated |
2007-8-2
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pubmed:abstractText |
Although oligodendrocytes undergo apoptosis after spinal cord injury, molecular mechanisms responsible for their death have been unknown. We report that oligodendrocyte apoptosis is regulated oppositely by c-Jun N-terminal kinase 3 (JNK3) and protein interacting with the mitotic kinase, never in mitosis A I (Pin1), the actions of which converge on myeloid cell leukemia sequence-1 (Mcl-1). Activated after injury, JNK3 induces cytochrome c release by facilitating the degradation of Mcl-1, the stability of which is maintained in part by Pin1. Pin1 binds Mcl-1 at its constitutively phosphorylated site, Thr163Pro, and stabilizes it by inhibiting ubiquitination. After injury JNK3 phosphorylates Mcl-1 at Ser121Pro, facilitating the dissociation of Pin1 from Mcl-1. JNK3 thus induces Mcl-1 degradation by counteracting the protective binding of Pin1. These results are confirmed by the opposing phenotypes observed between JNK3-/- and Pin1-/- mice: oligodendrocyte apoptosis and cytochrome c release are reduced in JNK3-/- but elevated in Pin1-/- mice. This report thus unveils a mechanism by which cytochrome c release is under the opposite control of JNK3 and Pin1, regulators for which the activities are intricately coupled.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 10,
http://linkedlifedata.com/resource/pubmed/chemical/NIMA-interacting peptidylprolyl...,
http://linkedlifedata.com/resource/pubmed/chemical/Peptidylprolyl Isomerase,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1529-2401
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8395-404
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pubmed:dateRevised |
2011-9-22
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pubmed:meshHeading |
pubmed-meshheading:17670986-Animals,
pubmed-meshheading:17670986-Apoptosis,
pubmed-meshheading:17670986-Mice,
pubmed-meshheading:17670986-Mice, Knockout,
pubmed-meshheading:17670986-Mice, Transgenic,
pubmed-meshheading:17670986-Mitogen-Activated Protein Kinase 10,
pubmed-meshheading:17670986-Oligodendroglia,
pubmed-meshheading:17670986-Peptidylprolyl Isomerase,
pubmed-meshheading:17670986-Spinal Cord Injuries,
pubmed-meshheading:17670986-Ubiquitin
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pubmed:year |
2007
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pubmed:articleTitle |
Opposite regulation of oligodendrocyte apoptosis by JNK3 and Pin1 after spinal cord injury.
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pubmed:affiliation |
Center for Molecular Neurobiology and Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, Ohio 43210, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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