Deed R W, Bianchi S M, Atherton G T, Johnston D, Santibanez-Koref M, Murphy J J, Norton J D
CRC Department of Gene Regulation, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Oncogene. 1993 Mar;8(3):599-607.
Transcription factors characterized by the presence of a helix-loop-helix (HLH) domain play a central role in the regulation of cell growth/differentiation and tumorigenesis. We report here the cDNA sequence of a human early-response gene, designated HLH 1R21, encoding a 15-kDa HLH protein that lacks a basic, DNA-binding domain and which by a number of criteria appears to be the human homologue of mouse HLH 462. Like its murine counterpart, HLH 1R21 protein functions as an Id (inhibitor of DNA binding) transcription factor by inhibiting the binding of E2A-containing protein complexes to muscle creatine kinase E-box enhancer oligonucleotide in vitro. However HLH 1R21 does not inhibit the binding of HLH Max protein to a Max-binding oligonucleotide in vitro, indicating that it has limited promiscuity in its ability to antagonize the function of other HLH transcription factors. In addition, HLH 1R21 mRNA transcripts are regulated by phorbol ester treatment of a diverse range of human cell lines and, when overexpressed in mouse NIH3T3 cells, HLH 1R21 induces a morphologically transformed phenotype.
以存在螺旋-环-螺旋（HLH）结构域为特征的转录因子在细胞生长/分化调控及肿瘤发生过程中发挥着核心作用。我们在此报告一个人类早期反应基因HLH 1R21的cDNA序列，该基因编码一种15 kDa的HLH蛋白，该蛋白缺乏碱性DNA结合结构域，并且根据多项标准似乎是小鼠HLH 462的人类同源物。与它的小鼠对应物一样，HLH 1R21蛋白在体外通过抑制含E2A的蛋白复合物与肌肉肌酸激酶E盒增强子寡核苷酸的结合，发挥Id（DNA结合抑制剂）转录因子的功能。然而，HLH 1R21在体外并不抑制HLH Max蛋白与Max结合寡核苷酸的结合，这表明它在拮抗其他HLH转录因子功能的能力方面具有有限的混杂性。此外，HLH 1R21 mRNA转录本受佛波酯处理多种人类细胞系的调控，并且当在小鼠NIH3T3细胞中过表达时，HLH 1R21诱导出形态转化表型。
