Moran Julie A, Dahl Erica L, Mulcahy R Timothy
Department of Pharmacology, University of Wisconsin Medical School, CSC K4/554, 600 Highland Avenue, Madison, WI 53792, USA.
Biochem J. 2002 Jan 15;361(Pt 2):371-7. doi: 10.1042/0264-6021:3610371.
The three small Maf proteins, MafF, MafG and MafK, have been implicated in a number of physiological processes, including development, differentiation, haematopoiesis and stress response. Here we report the constitutive expression of mafF, mafG and mafK in six human cell lines derived from various tissues (HepG2, IMR-32, K-562, HEK-293, RD and A549). The expression patterns of mafF, mafG and mafK varied widely among cell lines. Because small Maf proteins have been implicated in electrophile response element (EpRE)-mediated stress response, the ability of three EpRE activators [pyrrolidinedithiocarbamate (PDTC), phenylethyl isothiocyanate (PEITC) and t-butylhydroquinone (tBHQ)] to induce small Maf expression was examined in detail in HepG2 cells. Both PDTC and PEITC induced mafF, mafG and mafK expression, whereas tBHQ failed to markedly induce any of the three small Mafs. Where a response was observed, mafF was induced to the greatest extent compared with mafG and mafK, and this response was transcriptionally mediated. PDTC also induced small Maf expression in the other cell lines examined, with patterns of induction varying among cell lines. The differences in expression among the cell lines examined, coupled with the induction patterns observed, indicate that the three small maf genes are stress-responsive, but may be regulated via differing mechanisms. Furthermore, the fact that tBHQ, PDTC and PEITC induce EpRE activity, but that tBHQ fails to markedly induce any of the small Mafs, suggests that up-regulation of small Mafs is not an absolute requirement for EpRE-mediated gene expression.
三种小Maf蛋白,即MafF、MafG和MafK,参与了许多生理过程,包括发育、分化、造血和应激反应。在此,我们报告了mafF、mafG和mafK在源自不同组织的六种人类细胞系(HepG2、IMR-32、K-562、HEK-293、RD和A549)中的组成型表达。mafF、mafG和mafK的表达模式在不同细胞系中差异很大。由于小Maf蛋白与亲电反应元件(EpRE)介导的应激反应有关,因此在HepG2细胞中详细研究了三种EpRE激活剂[吡咯烷二硫代氨基甲酸盐(PDTC)、异硫氰酸苯乙酯(PEITC)和叔丁基对苯二酚(tBHQ)]诱导小Maf表达的能力。PDTC和PEITC均诱导mafF、mafG和mafK表达,而tBHQ未能显著诱导这三种小Maf中的任何一种。在观察到反应的情况下,与mafG和mafK相比,mafF的诱导程度最大,且这种反应是由转录介导的。PDTC还在其他检测的细胞系中诱导小Maf表达,诱导模式因细胞系而异。所检测细胞系之间表达的差异,以及观察到的诱导模式,表明这三个小maf基因是应激反应性的,但可能通过不同机制进行调控。此外,tBHQ、PDTC和PEITC诱导EpRE活性,但tBHQ未能显著诱导任何小Maf,这表明小Maf的上调不是EpRE介导的基因表达的绝对必要条件。