title: A novel role of CKIP-1 in promoting megakaryocytic differentiation.
abstract: 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.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.|Institute of Geriatrics, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Infectious Diseases, Chinese PLA 532 Hospital, Anhui 242700, China.
authors.forename: Yiwu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, General Hospital of Air Force of Chinese PLA, Beijing 100142, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.affiliation: Institute of Geriatrics, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics*; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D020014:K562 Cells; D007958:Leukocyte Count; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010976:Platelet Count; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020218:Response Elements
chemical_list: D050982:GATA1 Transcription Factor; D047908:Intracellular Signaling Peptides and Proteins; C408877:PLEKHO1 protein, human
keywords: CKIP-1; GATA-1; PMA; megakaryocytic differentiation; transcriptional regulation