A novel role of CKIP-1 in promoting megakaryocytic differentiation

作者：Fan, Jiao; Wang, Yiwu; Shen, Yuan; Liu, Qingyan; Gao, Rong; Qiu, Ya; Wang, Chanjuan; Zhang, Lingqiang^*

来源：Oncotarget, 2017, 8(18): 30138-30150.

DOI：10.18632/ncotarget.15619

• CKIP-1
• megakaryocytic differentiation
• PMA
• transcriptional regulation
• GATA-1

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.

• 出版日期2017-5-2
• 单位北京中医药大学; 蛋白质组学国家重点实验室; 中国人民解放军总医院; 中国人民解放军空军总医院; 中国人民解放军军事医学科学院