Upregulation of the constitutively expressed HSC70 by KLF4

Upregulation of the constitutively expressed HSC70 by KLF4
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KLF4 对 HSC70 组成型表达的上调

DOI:
10.1007/s12192-008-0033-5
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发表时间:
2008-04
影响因子:
3.8
通讯作者:
Liu, Meidong
Liu, Meidong
中科院分区:
生物学3区
文献类型:
--
作者:
Xiao, Xianzhong;Zhao, Jie;Zhang, Huali;Liu, Junwen;Liu, Ying;Liu, Meidong

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kr<s:1> ppel样因子4 (KLF4)是一种在从细菌到哺乳动物的各种生物中大量表达的转录因子。已经证明KLF4可以调控多种基因的表达。KLF4靶基因的分析揭示了其在细胞生长、增殖、分化、胚胎发生和炎症等方面的多种调控功能。然而,KLF4对诱导性热休克蛋白70 (HSP72)和热休克同源蛋白70 (HSP73)的表达调控尚不明确。在我们之前的研究中,互补脱氧核糖核酸芯片检测显示,KLF4过表达导致小鼠C2C12成肌细胞中HSP73信使核糖核酸(mRNA)显著上调,提示HSP73是KLF4调控的潜在靶基因。在KLF4过表达和KLF4缺陷细胞中,通过逆转录酶聚合酶链反应和Western blot进一步检测KLF4对HSP72和HSP73表达的影响。结果表明,在C2C12细胞和小鼠RAW264.7巨噬细胞中,KLF4过表达均可上调HSP73组成性表达;然而,在热应激反应中,KLF4过表达对HSP73水平的影响很小。此外,在正常情况下,通过morpholino反义寡核苷酸敲低内源性KLF4表达可显著降低HSP73 mRNA和蛋白水平。相反,KLF4对HSP72的表达没有影响。综上所述,这些发现表明KLF4作为HSP73组成表达的一种新的调节因子具有重要作用。
Krüppel-like factor 4 (KLF4) is a transcription factor that is abundantly expressed in various organisms from bacteria to mammals. It has been demonstrated that KLF4 regulates the expression of a wide range of genes. Analysis of KLF4 target genes reveals its diverse regulatory functions in cell growth, proliferation, differentiation, embryogenesis, and inflammation. However, the regulation of the expression of inducible heat shock protein 70 (HSP72) and heat shock cognate 70 (HSP73) by KLF4 is not defined. In our previous study, a complementary deoxyribonucleic acid microarray assay showed that KLF4 overexpression led to dramatic upregulation of HSP73 messenger ribonucleic acid (mRNA) in murine C2C12 myoblast cells, suggesting that HSP73 is a potential target gene regulated by KLF4. The effect of KLF4 on the expression of HSP72 and HSP73 was further examined by reverse transcriptase polymerase chain reaction and Western blot in KLF4-overexpressing or KLF4-deficient cells. The results showed the upregulation of the HSP73 constitutive expression by KLF4 overexpression in both C2C12 cells and murine RAW264.7 macrophages; in response to heat stress, however, few changes were observed in the levels of HSP73 by KLF4 overexpression. In addition, knockdown of endogenous KLF4 expression by morpholino antisense oligonucleotides significantly decreased both HSP73 mRNA and protein levels under normal conditions. Conversely, KLF4 had no effect on the expression of HSP72. Taken together, these findings suggest an important role for KLF4 as a novel regulator of the constitutive expression of HSP73.
DOI: 10.1080/01616412.1992.11740088
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