Ivashkiv L B, Fleming M D, Glimcher L H
Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115.
New Biol. 1992 Apr;4(4):360-8.
Transcription factors of the CREB/ATF family bind to a consensus DNA sequence TGACGTCA (cyclic AMP response element) found in the promoters of numerous genes. Transcriptional activation by one of these proteins, CREB, has been extensively analyzed, but the function of the other family members is not well understood. We have analyzed the function of mXBP (CRE-BP1, ATF-2), one member of the CREB/ATF family of transcription factors. Overexpression of mXBP resulted in the transcriptional activation of a promoter containing cAMP response elements which bind mXBP. Mutagenesis of the mXBP DNA-binding domain identified residues important for binding to the cyclic AMP response element. Mutants that did not bind specifically to DNA were not able to activate transcription. Several of these mutants suppressed both DNA binding and transcriptional activation by wild-type mXBP. These dominant negative mutants will be useful in further analysis of mXBP function.
CREB/ATF家族的转录因子可与众多基因启动子中发现的共有DNA序列TGACGTCA（环磷酸腺苷反应元件）相结合。其中一种蛋白CREB的转录激活作用已得到广泛分析，但其他家族成员的功能尚未被充分了解。我们分析了转录因子CREB/ATF家族成员之一mXBP（CRE - BP1，ATF - 2）的功能。mXBP的过表达导致含有可结合mXBP的环磷酸腺苷反应元件的启动子发生转录激活。mXBP DNA结合结构域的诱变确定了与环磷酸腺苷反应元件结合重要的残基。不能特异性结合DNA的突变体无法激活转录。其中一些突变体抑制了野生型mXBP的DNA结合和转录激活。这些显性负性突变体将有助于进一步分析mXBP的功能。
