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Open AccessArticle

The Phosphorylation of PDX-1 by Protein Kinase CK2 Is Crucial for Its Stability

1
Medical Biochemistry and Molecular Biology, Saarland University, 66424 Homburg, Germany
2
Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 156 Wujiadun, Hankou, Wuhan 430045, China
*
Author to whom correspondence should be addressed.
Academic Editor: Marc Le Borgne
Pharmaceuticals 2017, 10(1), 2; https://doi.org/10.3390/ph10010002
Received: 24 November 2016 / Revised: 20 December 2016 / Accepted: 23 December 2016 / Published: 28 December 2016
The homeodomain protein PDX-1 is a critical regulator of pancreatic development and insulin production in pancreatic β-cells. We have recently shown that PDX-1 is a substrate of protein kinase CK2; a multifunctional protein kinase which is implicated in the regulation of various cellular aspects, such as differentiation, proliferation, and survival. The CK2 phosphorylation site of PDX-1 is located within the binding region of the E3 ubiquitin ligase adaptor protein PCIF1. To study the interaction between PDX-1 and PCIF1 we used immunofluorescence analysis, co-immunoprecipitation, GST-pull-down studies, and proximity ligation assay (PLA). For the analysis of the stability of PDX-1 we performed a cycloheximide chase. We used PDX-1 in its wild-type form as well as phosphomutants of the CK2 phosphorylation site. In pancreatic β-cells PDX-1 binds to PCIF1. The phosphorylation of PDX-1 by CK2 increases the ratio of PCIF1 bound to PDX-1. The stability of PDX-1 is extended in the absence of CK2 phosphorylation. Our results identified protein kinase CK2 as new important modulator of the stability of PDX-1. View Full-Text
Keywords: pancreatic and duodenal homeobox protein PDX-1; PDX-1 C-terminus interacting factor PCIF1; protein kinase CK2; protein stability pancreatic and duodenal homeobox protein PDX-1; PDX-1 C-terminus interacting factor PCIF1; protein kinase CK2; protein stability
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Klein, S.; Meng, R.; Montenarh, M.; Götz, C. The Phosphorylation of PDX-1 by Protein Kinase CK2 Is Crucial for Its Stability. Pharmaceuticals 2017, 10, 2.

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