Opposite Regulation of Oligodendrocyte Apoptosis by JNK3 and Pin1 after Spinal Cord Injury
| Autor: | Chhavy Tep, Sung Ok Yoon, Kun Ping Lu, Takafumi Uchida, Xiao Zhen Zhou, Tae Y. Yune, Qi Ming Li |
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| Rok vydání: | 2007 |
| Předmět: |
Apoptosis
Mice Transgenic Article Mice Mitogen-Activated Protein Kinase 10 hemic and lymphatic diseases medicine Animals Mitosis Spinal Cord Injuries Mice Knockout Peptidylprolyl isomerase biology Ubiquitin Kinase General Neuroscience Cytochrome c Peptidylprolyl Isomerase Molecular biology Oligodendrocyte NIMA-Interacting Peptidylprolyl Isomerase Oligodendroglia medicine.anatomical_structure biology.protein PIN1 Signal transduction |
| Zdroj: | The Journal of Neuroscience. 27:8395-8404 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2478-07.2007 |
| Popis: | 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 cytochromecrelease 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 cytochromecrelease are reduced in JNK3−/−but elevated in Pin1−/−mice. This report thus unveils a mechanism by which cytochromecrelease is under the opposite control of JNK3 and Pin1, regulators for which the activities are intricately coupled. |
| Databáze: | OpenAIRE |
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