A novel role of CKIP-1 in promoting megakaryocytic differentiation
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Jiao Fan1,2, Yiwu Wang3, Yuan Shen4, Qingyan Liu5, Rong Gao6, Ya Qiu2, Chanjuan Wang1, Lingqiang Zhang1
1State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China
2Institute of Geriatrics, Chinese PLA General Hospital, Beijing 100853, China
3Department of Infectious Diseases, Chinese PLA 532 Hospital, Anhui 242700, China
4Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing 100850, China
5Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, China
6Department of Pharmacy, General Hospital of Air Force of Chinese PLA, Beijing 100142, China
Lingqiang Zhang, email: firstname.lastname@example.org
Keywords: CKIP-1, megakaryocytic differentiation, PMA, transcriptional regulation, GATA-1
Received: November 10, 2016 Accepted: January 27, 2017 Published: February 22, 2017
Casein kinase 2-interacting protein-1 (CKIP-1) is a known regulator of cardiomyocytes and macrophage proliferation. In this study, we showed that CKIP-1 was involved in the process of megakaryocytic differentiation. During megakaryocytic differentiation of K562 cells, CKIP-1 was dramatically upregulated and this upregulation induced by PMA was mediated through downregulation of transcription factor GATA-1. By transient transfection, oligonucleotide-directed mutagenesis and chromatin immunoprecipitation assays, we identified the transcriptional regulation of CKIP-1 by GATA-1. Overexpression of CKIP-1 initiated events of spontaneous megakaryocytic differentiation in K562 cells. Conversely, knockdown of CKIP-1 in cell lines suppressed megakaryocytic differentiation. Mechanistically, overexpression of CKIP-1 changed the expression levels of transcription factors that have been shown to be critical in erythro-megakaryocytic differentiation such as Fli-1, c-Myb and c-Myc. In vivo analysis confirmed that CKIP-1-/- mice had decreased number of CD41+ cells harvested from bone marrow, and lower platelet levels when compared to wild-type littermates. This is the first direct evidence suggesting that CKIP-1 is a novel regulator of megakaryocytic differentiation.
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