Regulation of tyrosinase gene expression by cAMP in B16 melanoma cells involves two CATGTG motifs surrounding the TATA box: implication of the microphthalmia gene product.
Regulation of tyrosinase gene expression by cAMP in B16 melanoma cells involves two CATGTG motifs surrounding the TATA box: implication of the microphthalmia gene product.
复制标题
DOI：
10.1083/jcb.134.3.747
复制
发表时间：
1996-08
影响因子：
7.8
通讯作者：
Ballotti, R
中科院分区：
文献类型：
--
作者：
Bertolotto, C;Bille, K;Ortonne, JP;Ballotti, R
在黑素细胞和黑色素瘤细胞中，通过cAMP升高剂上调黑素生成是由于酪氨酸酶活性的刺激引起的，这归因于酪氨酸酶蛋白和信使量的增加。然而，cAMP升高剂增加酪氨酸酶mRNA的机制仍有待阐明。在这项研究中，使用含有小鼠酪氨酸酶基因转录起始位点5'端的2.2 kb片段的荧光素酶报告质粒，我们表明cAMP升高剂导致酪氨酸酶启动子转录活性的强烈刺激（20倍）。小鼠酪氨酸酶启动子的缺失和突变表明，M-box 70 bp上游的TATA框和E-box位于下游的TATA框，附近的起始位点，参与调节酪氨酸酶启动子活性的cAMP。此外，我们发现，小眼症，b-HLH转录因子与色素沉着疾病的小鼠，结合到这些调控元件和调节酪氨酸酶启动子的转录活性。由于cAMP刺激小眼症的M盒和E盒的结合，这是诱人的建议，小眼症，通过其与周围的TATA盒的顺式作用元件的相互作用，在调节小鼠酪氨酸酶基因表达的cAMP中起着关键作用。
In melanocytes and in melanoma cells, upregulation of melanogenesis, by cAMP elevating agents, results from a stimulation of tyrosinase activity that has been ascribed to an increase in tyrosinase protein and messenger amount. However, the mechanism by which cAMP elevating agents increase tyrosinase mRNA remains to be elucidated. In this study, using a luciferase reporter plasmid containing the 2.2-kb fragment 5' of the transcriptional start site of the mouse tyrosinase gene, we showed that cAMP elevating agents lead to a strong stimulation (20-fold) of transcriptional activity of the tyrosinase promoter. Deletions and mutations in the mouse tyrosinase promoter showed that the M-box 70-bp upstream from the TATA-box and the E-box located downstream the TATA-box, near to the initiator site, are involved in the regulation of the tyrosinase promoter activity by cAMP. Additionally, we showed that microphthalmia, a b-HLH transcription factor associated with pigmentation disorders in mouse, binds to these regulatory elements and modulates the transcriptional activity of the tyrosinase promoter. Since cAMP stimulates the binding of microphthalmia to the M-box and to the E-box; it is tempting to propose that microphthalmia, through its interaction with cis-acting elements surrounding the TATA-box, plays a key role in the regulation of the mouse tyrosinase gene expression by cAMP.
登录
查看更多内容
影响因子：
5.3
作者：
BENTLEY, NJ;EISEN, T;GODING, CR
通讯作者：
GODING, CR
影响因子：
30.8
作者：
HUGHES, AE;NEWTON, VE;READ, AP
通讯作者：
READ, AP
影响因子：
64.5
作者：
HODGKINSON, CA;MOORE, KJ;ARNHEITER, H
通讯作者：
ARNHEITER, H
影响因子：
10.5
作者：
GREGOR, PD;SAWADOGO, M;ROEDER, RG
通讯作者：
ROEDER, RG
影响因子：
11.4
作者：
JACKSON, IJ;CHAMBERS, DM;HEARING, V
通讯作者：
HEARING, V