Department of Biochemistry and State Key Laboratory for Liver Research, LKS Faculty of Medicine, The University of Hong Kong.
Cell Biosci. 2011 Feb 17;1(1):6. doi: 10.1186/2045-3701-1-6.
The CREB3 subfamily of membrane-bound bZIP transcription factors has five members in mammals known as CREB3 and CREB3L1-L4. One current model suggests that CREB3 subfamily transcription factors are similar to ATF6 in regulated intramembrane proteolysis and transcriptional activation. Particularly, they were all thought to be proteolytically activated in response to endoplasmic reticulum (ER) stress to stimulate genes that are involved in unfolded protein response (UPR). Although the physiological inducers of their proteolytic activation remain to be identified, recent findings from microarray analyses, RNAi screens and gene knockouts not only demonstrated their critical roles in regulating development, metabolism, secretion, survival and tumorigenesis, but also revealed cell type-specific patterns in the activation of their target genes. Members of the CREB3 subfamily show differential activity despite their structural similarity. The spectrum of their biological function expands beyond ER stress and UPR. Further analyses are required to elucidate the mechanism of their proteolytic activation and the molecular basis of their target recognition.
膜结合 bZIP 转录因子的 CREB3 亚家族在哺乳动物中有 5 个成员，分别称为 CREB3 和 CREB3L1-L4。目前的一个模型表明，CREB3 亚家族转录因子在调节跨膜蛋白水解和转录激活方面与 ATF6 相似。特别是，它们都被认为是在受到内质网（ER）应激时通过蛋白水解激活的，以刺激参与未折叠蛋白反应（UPR）的基因。尽管它们蛋白水解激活的生理诱导物仍有待确定，但最近的微阵列分析、RNAi 筛选和基因敲除的发现不仅证明了它们在调节发育、代谢、分泌、存活和肿瘤发生中的关键作用，还揭示了其靶基因激活的细胞类型特异性模式。尽管 CREB3 亚家族成员的结构相似，但它们的活性却存在差异。它们的生物学功能范围超出了 ER 应激和 UPR。需要进一步分析来阐明它们的蛋白水解激活机制和靶标识别的分子基础。
