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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
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Jade-1S phosphorylation induced by CK1α contributes to cell cycle progression
Lori Borgal1,2, Markus M Rinschen1,2,3, Claudia Dafinger1,2
1a Department II of Internal Medicine ; University of Cologne ; Cologne , Germany.
Cell Cycle (Georgetown, Tex.)
|February 27, 2016
Summary
CK1α phosphorylation of Jade-1S protein acts as a molecular switch, regulating chromatin remodeling and cell cycle progression. This finding may illuminate mechanisms of kidney epithelial injury repair.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Jade-1S, a PHD zinc finger protein, is part of the HBO1 histone acetyltransferase complex and binds chromatin.
- Jade-1S functions as an E3 ubiquitin ligase for β-catenin and is regulated by CK1α phosphorylation.
Purpose of the Study:
- To investigate the functional consequences of CK1α-mediated phosphorylation on Jade-1S.
- To elucidate the role of Jade-1S phosphorylation in regulating chromatin binding and cell cycle progression.
Main Methods:
- Stable expression of wild-type and mutant Jade-1S (lacking CK1α phosphorylation motif).
- Interactome analyses to identify binding partners.
- Phosphoproteomic analyses to identify phosphorylation sites.
Main Results:
- A Jade-1S mutant, unphosphorylatable by CK1α, showed increased binding to chromatin remodeling and transcriptional repression proteins.
- Cells expressing the mutant exhibited delayed cell cycle progression and elongated shape.
- CK1α phosphorylation of Jade-1S creates a PLK1 phospho-binding domain, suggesting a regulatory switch.
Conclusions:
- CK1α phosphorylation of Jade-1S acts as a molecular switch, inhibiting chromatin remodeling functions and promoting cell cycle progression.
- Altered Jade-1S expression in kidney injury suggests a role in epithelial repair mechanisms.
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