دورية أكاديمية
Hippo Signaling Pathway Dysregulation in Human Huntington's Disease Brain and Neuronal Stem Cells.
العنوان: | Hippo Signaling Pathway Dysregulation in Human Huntington's Disease Brain and Neuronal Stem Cells. |
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المؤلفون: | Mueller KA; NeuroEpigenetics Laboratory, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Boston, MA, 02129-4404, USA., Glajch KE; NeuroEpigenetics Laboratory, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Boston, MA, 02129-4404, USA., Huizenga MN; NeuroEpigenetics Laboratory, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Boston, MA, 02129-4404, USA., Wilson RA; NeuroEpigenetics Laboratory, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Boston, MA, 02129-4404, USA., Granucci EJ; NeuroEpigenetics Laboratory, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Boston, MA, 02129-4404, USA., Dios AM; NeuroEpigenetics Laboratory, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Boston, MA, 02129-4404, USA., Tousley AR; Cellular Neurobiology Laboratory, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Boston, MA, 02129-4404, USA., Iuliano M; Cellular Neurobiology Laboratory, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Boston, MA, 02129-4404, USA., Weisman E; Cellular Neurobiology Laboratory, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Boston, MA, 02129-4404, USA., LaQuaglia MJ; Department of Surgery, Boston Children's Hospital, Boston, USA., DiFiglia M; Cellular Neurobiology Laboratory, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Boston, MA, 02129-4404, USA., Kegel-Gleason K; Cellular Neurobiology Laboratory, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Boston, MA, 02129-4404, USA., Vakili K; Department of Surgery, Boston Children's Hospital, Boston, USA., Sadri-Vakili G; NeuroEpigenetics Laboratory, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Boston, MA, 02129-4404, USA. gsadrivakili@mgh.harvard.edu. |
المصدر: | Scientific reports [Sci Rep] 2018 Jul 27; Vol. 8 (1), pp. 11355. Date of Electronic Publication: 2018 Jul 27. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
مواضيع طبية MeSH: | Signal Transduction*, Brain/*pathology , Huntington Disease/*metabolism , Huntington Disease/*pathology , Neural Stem Cells/*metabolism , Protein Serine-Threonine Kinases/*metabolism, 14-3-3 Proteins/metabolism ; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Disease Models, Animal ; Hippo Signaling Pathway ; Humans ; Neural Stem Cells/pathology ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; Phosphorylation ; Protein Binding ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Transcription Factors ; Transcription, Genetic ; YAP-Signaling Proteins |
مستخلص: | The Hippo signaling pathway is involved in organ size regulation and tumor suppression. Although inhibition of Hippo leads to tumorigenesis, activation of Hippo may play a role in neurodegeneration. Specifically, activation of the upstream regulator, mammalian sterile 20 (STE20)-like kinase 1 (MST1), reduces activity of the transcriptional co-activator Yes-Associated Protein (YAP), thereby mediating oxidative stress-induced neuronal death. Here, we investigated the possible role of this pathway in Huntington's disease (HD) pathogenesis. Our results demonstrate a significant increase in phosphorylated MST1, the active form, in post-mortem HD cortex and in the brains of CAG knock-in Hdh Q111/Q111 mice. YAP nuclear localization was also decreased in HD post-mortem cortex and in neuronal stem cells derived from HD patients. Moreover, there was a significant increase in phosphorylated YAP, the inactive form, in HD post-mortem cortex and in Hdh Q111/Q111 brain. In addition, YAP was found to interact with huntingtin (Htt) and the chaperone 14-3-3, however this interaction was not altered in the presence of mutant Htt. Lastly, YAP/TEAD interactions and expression of Hippo pathway genes were altered in HD. Together, these results demonstrate that activation of MST1 together with a decrease in nuclear YAP could significantly contribute to transcriptional dysregulation in HD. |
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المشرفين على المادة: | 0 (14-3-3 Proteins) 0 (Adaptor Proteins, Signal Transducing) 0 (Phosphoproteins) 0 (RNA, Messenger) 0 (Transcription Factors) 0 (YAP-Signaling Proteins) 0 (YAP1 protein, human) EC 2.7.11.1 (Protein Serine-Threonine Kinases) |
تواريخ الأحداث: | Date Created: 20180729 Date Completed: 20191016 Latest Revision: 20211204 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC6063913 |
DOI: | 10.1038/s41598-018-29319-4 |
PMID: | 30054496 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2045-2322 |
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DOI: | 10.1038/s41598-018-29319-4 |