TARGETED MUTATION OF THE CREB GENE - COMPENSATION WITHIN THE CREB/ATF FAMILY OF TRANSCRIPTION FACTORS
TARGETED MUTATION OF THE CREB GENE - COMPENSATION WITHIN THE CREB/ATF FAMILY OF TRANSCRIPTION FACTORS
复制标题
DOI：
10.1073/pnas.91.12.5647
复制
发表时间：
1994-06-07
影响因子：
11.1
通讯作者：
SCHUTZ, G
中科院分区：
文献类型：
--
作者：
HUMMLER, E;COLE, TJ;SCHUTZ, G
cAMP反应元件结合蛋白（CREB）已被认为是许多基因转录调控的关键调节因子。为了评估CREB在体内的功能重要性及其在发育中的作用，我们使用基因靶向来产生具有CREB基因破坏的小鼠。纯合子突变小鼠看起来健康，没有表现出生长或发育受损。在这份报告中，我们证明，CREB和其他两个成员的CREB/ATF家族，cAMP反应元件调节蛋白（CREM）和激活转录因子1（ATF 1），似乎形成一个独特的亚组内这一广泛的转录因子类。CREB突变小鼠CREM mRNA和蛋白水平的检查表明CREM在所有检查的组织中过表达，但ATF 1水平没有变化。这些数据表明，CREB不是cAMP依赖性转录调控的唯一介质，并且可能与cAMP反应元件结合蛋白的特定子集协同作用以抑制cAMP信号，并且在其不存在的情况下，这些相同的蛋白质可以补偿CREB在体内的功能。
The cAMP response element binding protein (CREB) has been implicated as a key regulator in the transcriptional control of many genes. To assess the functional importance of CREB in vivo and its role in development, we used gene targeting to generate mice with a disruption of the CREB gene. Homozygous mutant mice appeared healthy and exhibited no impairment of growth or development. In this report we demonstrate that CREB and two other members of the CREB/ATF family, cAMP response element modulation protein (CREM) and activating transcription factor 1 (ATF1), appear to form a unique subgroup within this extensive class of transcription factors. Examination of CREM mRNA and protein levels in CREB mutant mice demonstrated overexpression of CREM in all tissues examined, but no change in ATF1 levels. These data demonstrate that CREB is not the sole mediator of cAMP-dependent transcriptional regulation and probably acts in concert with a specific subset of cAMP response element-binding proteins to transduce the cAMP signal and, in its absence, these same proteins can compensate for CREB function in vivo.