Abnormal expression of mouse mast cell protease 5 gene in cultured mast cells derived from mutant mi/mi mice
Abnormal expression of mouse mast cell protease 5 gene in cultured mast cells derived from mutant mi/mi mice
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DOI：
10.1182/blood.v90.8.3057
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发表时间：
1997-10-15
期刊：
影响因子：
20.3
通讯作者：
Kitamura, Y
中科院分区：
文献类型：
--
作者：
Morii, E;Jippo, T;Kitamura, Y
肥大细胞含有大量肥大细胞特有的蛋白酶。我们已经报道，在mi/mi突变小鼠的培养肥大细胞(CMCs)和皮肤肥大细胞中，小鼠肥大细胞蛋白6(MMCP-6)的表达都显著降低。在本研究中，我们发现MMCP-5在MI/MI小鼠皮肤肥大细胞中表达降低，但在皮肤肥大细胞中不表达，并比较了MMCP-5和MMCP-6的调节机制。Mi基因编码碱性-螺旋-环-亮氨酸拉链(bHLH-Zip)蛋白家族转录因子(以下简称MITF)的成员。BHLH-Zip转录因子识别和结合的共有序列为CANNTG。正常(+)MITF的过表达而不是mi-MITF的过表达使MMCP-5基因在mi/mi CMCs中的低表达正常化，表明+-MITF参与了MMCP-5基因的反式激活。虽然+-MITF直接与MMCP-6基因启动子区域的CANNTG基序结合并反式激活MMCP-6基因，但未检测到+-MITF与MMCP-5基因启动子区域的CAGTTG基序的结合，但+-MITF似乎间接调节MMCP-5基因的反式激活。此外，在Mi/mi CMCs中加入干细胞因子可使MMCP-5基因的表达正常化，但不能使MMCP-6基因的表达正常化。虽然MMCP-5和MMCP-6在MI/MI细胞中的表达均显著降低，但它们的调节机制似乎不同。(C)1997年由美国血液病学会主办。
Mast cells contain a lot of mast cell-specific proteases. We have reported that the expression of mouse mast cell protease 6 (MMCP-6) is remarkably reduced in both cultured mast cells (CMCs) and skin mast cells of mi/mi mutant mice. In the present study, we found that the expression of MMCP-5 was reduced in CMCs but not in skin mast cells of mi/mi mice, and we compared the regulation mechanisms of MMCP-5 with those of MMCP-6. The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). The consensus sequence recognized and bound by bHLH-Zip transcription factors is CANNTG. The overexpression of the normal (+) MITF but not of mi-MITF normalized the poor expression of the MMCP-5 gene in mi/mi CMCs, indicating the involvement of +-MITF in transactivation of the MMCP-5 gene. Although +-MITF directly bound CANNTG motifs in the promoter region of the MMCP-6 gene and transactivated it, the binding of +-MITF to the CAGTTG motif in the promoter region of the MMCP-5 gene was not detectable, The +-MITF appeared to regulate the transactivation of the MMCP-5 gene indirectly. Moreover, addition of stem cell factor to the medium normalized the expression of the MMCP-5 but not of the MMCP-6 gene in mi/mi CMCs. Despite the significant reduction of both MMCP-5 and MMCP-6 expressions in mi/mi CMCs, their regulation mechanisms appeared to be different. (C) 1997 by The American Society of Hematology.