title: Zinc finger protein HZF1 promotes K562 cell proliferation by interacting with and inhibiting INCA1.
abstract: Previously, we characterized a zinc finger protein gene HZF1 (ZNF16) and demonstrated that it played a significant role in the erythroid and megakaryocytic differentiation of K562 cells by knockdown of the gene. In this study, we examined the effect of HZF1 on the proliferation and apoptosis of K562 cells and identified the possible mechanism for this effect. By lentivirus-mediated gene transfer, we obtained stable K562 transductants with HZF1 overexpression (K562/WPXL-HZF1) and stable control transductants (K562/WPXL). Significantly rapid cell amplification was observed in K562/WPXL-HZF1 cells compared to K562/WPXL cells. The cell cycles of the two transductants were analyzed and the results demonstrated that HZF1 overexpression promoted the S to G2/M phase transition. Additionally, we found that the overexpression of HZF1 slightly inhibits the apoptosis of K562 cells induced by sodium arsenate. Furthermore, using a yeast two-hybrid (Y2H) system we identified the HZF1-interacting proteins and screened 29 potential binding partners of HZF1. Using a co-immunoprecipitation (Co-IP) assay, we confirmed the interaction between HZF1 and the inhibitor of cyclin-dependent kinase (CDK) interacting with cyclin A1 (INCA1), and proved that this interaction leads to the inhibition of INCA1 function, which rescued the activity of CDK2 inhibited by INCA1. In conclusion, our results identified novel functions of the HZF1 gene and revealed a possible mechanism through which HZF1 affects K562 cell proliferation.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Deng
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Zhan-Wen
authors.initials: ZW
authors.lastname: Du
authors.forename: Jun-Wu
authors.initials: JW
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D001149:Arsenates / Q000633:toxicity; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002455:Cell Division; D049109:Cell Proliferation; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016195:G2 Phase; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D020014:K562 Cells; D016086:Lentivirus / Q000235:genetics; D010750:Phosphoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D001149:Arsenates; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C492512:INCA1 protein, human; D010750:Phosphoproteins; C514335:ZNF266 protein, human; C009277:sodium arsenate; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2