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Wdr68 Is Required for Dyrk1a Expression Independent of Major Proteasome Pathways
Başlık:
Wdr68 Is Required for Dyrk1a Expression Independent of Major Proteasome Pathways
Yazar:
Xu, Jingyi, author.
ISBN:
9780438070813
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (51 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Advisors: Robert Nissen Committee members: Eric Wood; Howard Xu.
Özet:
Overexpression of dual-specificity tyrosine phosphorylation-regulated kinase (Dyrk1a) contributes to the neurodevelopmental defects in Down Syndrome and Alzheimer's disease. WD repeat protein 68 /DDB1 and CUL4 associated factor 7 (Wdr68 or Dcaf7, hereafter Wdr68) functions to drive craniofacial development, and as a scaffolding protein, it interacts with Dyrk1a. Previously, in HeLa and C2C12 wdr68 knockout sublines, Western blots showed lack of Dyrk1a protein expression, relative to non-target sublines. Overexpression of Wdr68 restored Dyrk1a in wdr68 knockout cells and enhanced Dyrk1a expression in non-target sublines. qRT-PCR revealed that Wdr68 had no effect on Dyrk1a mRNA expression, therefore Wdr68 was required for Dyrk1a via a post-transcriptional mechanism. In this study, to test if overexpression of Dyrk1a will not affect Wdr68, I overexpressed Dyrk1a in HeLa non-target (NT2) cells and the expression level of Wdr68 did not change. To test if the expression level of Wdr68 directly predicts the expression level of Dyrk1a, I detected expression levels of Wdr68 and Dyrk1a from HeLa NT2 cells, HeLa wdr68 knockout cells, C2C12 NT cells, and C2C12 wdr68-knockdown cells. The results suggest a simple positive correlation between Wdr68 level and Dyrk1a level. To test if proteolytic degradation of Dyrk1a might occur in wdr68 knockout cells, I used the ubiquitin-proteasome inhibitor MG132. MG132 did not restore Dyrk1a in HeLa wdr68 knockout cells. I also used autophagy inhibitor Chloroquine (CQ) but CQ did not restore Dyrk1a in wdr68 knockout cells either. Taken together, these data suggest that reduced Dyrk1a expression in wdr68 knockout cells is proteasome independent.
Notlar:
School code: 0962
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(692836.1) | 692836-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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