The Basal Promoters for the Human Reduced Folate Carrier Gene Are Regulated by a GC-box and a cAMP-response Element/AP-1-like Element
The Basal Promoters for the Human Reduced Folate Carrier Gene Are Regulated by a GC-box and a cAMP-response Element/AP-1-like Element
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人类还原叶酸载体基因的基础启动子由 GC 盒和 cAMP 响应元件/AP-1 样元件调节
DOI：
--
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发表时间：
2001
影响因子：
4.8
通讯作者：
L. Matherly
中科院分区：
文献类型：
--
作者：
J. Whetstine;L. Matherly
我们的实验室先前鉴定了人还原叶酸载体（hRFC）基因的两个功能性启动子（指定为A和B），其导致具有不同5′-非翻译区的hRFC转录物。通过瞬时转染HT 1080和HepG 2细胞，在hRFC-B和hRFC-A启动子上分别进行一系列5′和3′缺失，最小启动子分别定位在46和47个碱基对内。凝胶迁移率变动分析与hRFC-B的基础启动子区域揭示了特定的DNA-蛋白质复合物涉及一个高度保守的GC盒和Sp1或Sp3。在果蝇SL 2细胞中，Sp1和长Sp3亚型都能有效地反式激活hRFC-B基础启动子;然而，短Sp3亚型在转录上是惰性的，并导致Sp1反式激活的有效抑制。对于hRFC-A基础启动子，CRE/AP-1样元件被DNA结合蛋白的bZip超家族结合。鉴定hRFC-A的细胞特异性DNA-蛋白质复合物（HT 1080细胞中的CREB-1和c-Jun; HepG 2细胞中的CREB-1和ATF-1）。当GC盒和CRE/AP-1样元件突变时，在两种细胞系中观察到启动子活性降低60-90%。这些结果确定了hRFC基础启动子的关键调控区域，并强调了Sp和bZip家族转录因子在调控hRFC表达中的功能重要性。
Our laboratory previously identified two functional promoters (designated A and B) for the human reduced folate carrier (hRFC) gene that result in hRFC transcripts with differing 5′-untranslated regions. By transiently transfecting HT1080 and HepG2 cells with a series of 5′ and 3′ deletions in the hRFC-B and -A promoters, the minimal promoters were localized within 46 and 47 base pairs, respectively. Gel mobility shift assays with the hRFC-B basal promoter region revealed specific DNA-protein complexes involving a highly conserved GC-box and Sp1 or Sp3. In Drosophila SL2 cells, both Sp1 and the long Sp3 isoform potently transactivated the hRFC-B basal promoter; however, the short Sp3 isoforms were transcriptionally inert and resulted in a potent inhibition of Sp1 transactivation. For the hRFC-A basal promoter, a CRE/AP-1-like element was bound by the bZip superfamily of DNA-binding proteins. Cell-specific DNA-protein complexes were identified for hRFC-A (CREB-1 and c-Jun in HT1080 cells; CREB-1 and ATF-1 in HepG2 cells). When the GC-box and CRE/AP-1-like elements were mutated, a 60–90% decrease in promoter activity was observed in both cell lines. These results identify the critical regulatory regions for the hRFC basal promoters and stress the functional importance of the Sp and bZip families of transcription factors in regulating hRFC expression.
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DOI：
10.1016/s0021-9258(18)61070-1
发表时间：
1987-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
P. Matsudaira
通讯作者：
P. Matsudaira
影响因子：
20.3
作者：
Gorlick, R;Goker, E;Bertino, JR
通讯作者：
Bertino, JR
编码叶酸转运蛋白的鼠 RFC-1 基因的组织、结构和可变剪接。
影响因子：
3.5
作者：
Tolner,B;Roy,K;Sirotnak,FM
通讯作者：
Sirotnak,FM
影响因子：
14.9
作者：
Kennett, SB;Udvadia, AJ;Horowitz, JM
通讯作者：
Horowitz, JM
甲氨蝶呤耐药鼠 L1210 白血病细胞系中甲氨蝶呤转运载体易位存在功能缺陷的证据。
DOI：
--
发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Schuetz,JD;Matherly,LH;Westin,EH;Goldman,ID
通讯作者：
Goldman,ID