生物
锌指
交易激励
转录因子
甲状腺髓样癌
分子生物学
癌症研究
增强子
发起人
细胞分化
锌指转录因子
LIM域
基因
细胞生物学
基因表达
甲状腺癌
甲状腺
遗传学
作者
Arunthathi Thiagalingam,A de Bustros,Michael Borges,Ravirasmi Jasti,Debra L Compton,Lisa E. Diamond,Mack Mabry,Douglas W. Ball,Stephen B. Baylin,Barry D. Nelkin
标识
DOI:10.1128/mcb.16.10.5335
摘要
An activated ras oncogene induces a program of differentiation in the human medullary thyroid cancer cell line TT. This differentiation process is accompanied by a marked increase in the transcription of the human calcitonin (CT) gene. We have localized a unique Ras-responsive transcriptional element (RRE) in the CT gene promoter. DNase I protection indicates two domains of protein-DNA interaction, and each domain separately can confer Ras-mediated transcriptional inducibility. This bipartite RRE was also found to be Raf responsive. By affinity screening, we have cloned a cDNA coding for a zinc finger transcription factor (RREB-1) that binds to the distal RRE. The consensus binding site for this factor is CCCCAAACCACCCC. RREB-1 is expressed ubiquitously in human tissues outside the adult brain. Overexpression of RREB-1 protein in TT cells confers the ability to mediate increased transactivation of the CT gene promoter-reporter construct during Ras- or Raf-induced differentiation. These data suggest that RREB-1 may play a role in Ras and Raf signal transduction in medullary thyroid cancer and other cells.
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