Hsu J C, Laz T, Mohn K L, Taub R
Department of Human Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104-6145.
Proc Natl Acad Sci U S A. 1991 May 1;88(9):3511-5. doi: 10.1073/pnas.88.9.3511.
Liver regeneration provides one of the few systems for analysis of mitogenesis in the fully developed, intact animal. Several proteins have been identified as part of the primary growth response in regenerating liver and in mitogen-stimulated cells. Some of these proteins, such as the Jun and Fos families of transcription factors, are thought to have a role in activating transcription of genes expressed subsequently in the growth response. Through differential screening of a regenerating-liver cDNA library, we have identified a rapidly and highly induced gene encoding a 21-kDa leucine-zipper-containing protein that we have designated liver regeneration factor 1 (LRF-1). LRF-1 has no homology with other leucine-zipper proteins outside the basic and leucine-zipper domains. LRF-1 alone can bind DNA, but it preferentially forms heteromeric complexes with c-Jun and Jun-B and does not interact with c-Fos. In solution, it binds with highest affinity to cAMP response elements but also has affinity for related sites. In cotransfection studies, LRF-1 in combination with c-Jun strongly activates a c-Jun-responsive promoter. The induction of the LRF-1 gene in regenerating liver greatly increases the potential variety of heterodimeric combinations of leucine-zipper transcription factors. While LRF-1 mRNA is rapidly induced in the absence of protein synthesis, its peak induction is later than c-fos mRNA, suggesting that LRF-1 may regulate responsive genes at a later point in the cell cycle. As such, LRF-1 may have a unique and critical role in growth regulation of regenerating liver and mitogen-stimulated cells.
肝脏再生为在完全发育的完整动物中分析有丝分裂提供了为数不多的系统之一。几种蛋白质已被确定为再生肝脏和有丝分裂原刺激细胞中初级生长反应的一部分。其中一些蛋白质，如转录因子Jun和Fos家族，被认为在激活生长反应中随后表达的基因转录方面发挥作用。通过对再生肝脏cDNA文库的差异筛选，我们鉴定出一个快速且高度诱导的基因，该基因编码一种21 kDa含亮氨酸拉链的蛋白质，我们将其命名为肝脏再生因子1（LRF-1）。LRF-1在基本结构域和亮氨酸拉链结构域之外与其他含亮氨酸拉链的蛋白质没有同源性。单独的LRF-1可以结合DNA，但它优先与c-Jun和Jun-B形成异源复合物，而不与c-Fos相互作用。在溶液中，它与cAMP反应元件结合的亲和力最高，但对相关位点也有亲和力。在共转染研究中，LRF-1与c-Jun联合强烈激活c-Jun反应性启动子。再生肝脏中LRF-1基因的诱导极大地增加了含亮氨酸拉链转录因子异源二聚体组合的潜在多样性。虽然LRF-1 mRNA在没有蛋白质合成的情况下迅速诱导，但其诱导峰值晚于c-fos mRNA，这表明LRF-1可能在细胞周期的后期调节反应性基因。因此，LRF-1可能在再生肝脏和有丝分裂原刺激细胞的生长调节中具有独特而关键的作用。
