KLF7 promotes preadipocyte proliferation via activation of the Akt signaling pathway by Cis-regulating CDKN3  

作　　者：Ziqiu Jia Zhao Jin Shuli Shao Hu Xu Wen Li Mahmood Khan Weiyu Wang Weiwei Zhang Yingning Sun 

机构地区：[1]College of Life Science and Agriculture Forestry,Qiqihar University,Qiqihar 161006,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第10期1486-1496,共11页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(No.31402061);the Heilongjiang Provincial Natural Science Foundation of China(No.YQ2019C025);the Program of Graduate Student Innovation and Scientific Research(No.YJSCX2020043);the Project of the Basic Business of Heilongjiang Provincial Education Department(No.YSTSXK201875).

摘　　要：Krüppel-like transcription factor 7(KLF7)promotes preadipocyte proliferation;however,its target gene in this process has not yet been identified.Using KLF7 ChIP-seq analysis,we previously showed that a KLF7-binding peak is present upstream of the cyclin-dependent kinase inhibitor 3 gene(CDKN3)in chicken preadipocytes.In the present study,we identify CDKN3 as a target gene of KLF7 that mediates the effects of KLF7 on preadipocyte proliferation.Furthermore,5′-truncating mutation analysis shows that the minimal promoter is located between nt–160 and nt–7(relative to the translation initiation codon ATG)of CDKN3.KLF7 overexpression increases CDKN3 promoter activity in the DF-1 and immortalized chicken preadipocyte(ICP1)cell lines.Deletion of the putative binding site of KLF7 abolishes the promotive effect of KLF7 overexpression on CDKN3 promoter activity.Moreover,CDKN3 knockdown and overexpression assays reveal that CDKN3 enhances ICP1 cell proliferation.Flow cytometry analysis shows that CDKN3 accelerates the G1/S transition.Furthermore,we find that KLF7 promotes ICP1 cell proliferation via Akt phosphorylation by regulating CDKN3.Taken together,our results suggest that KLF7 promotes preadipocyte proliferation by activating the Akt signaling pathway by cis-regulating CDKN3,thus driving the G1/S transition.

关 键 词：PROLIFERATION cyclin-dependent kinase inhibitor 3 Krüppel-like transcription factor 7 Akt signaling pathway PREADIPOCYTE 

分 类 号：Q5[生物学—生物化学]