Pennypacker K R
Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, Tampa, USA.
J Fla Med Assoc. 1995 Aug;82(8):551-4.
Transcription factors are regulatory proteins that modify gene expression. Any cellular function requiring alterations in mRNA levels depends upon these factors. The CNS, AP-1 (activator protein-1; c-fos and fos-related antigens plus jun-related factors) and CREB (cAMP responsive element binding protein) families of transcription factors have been extensively studied. The DNA binding complex is composed of dimers formed between the AP-1 and CREB factors and binding specificity is dictated by which proteins comprise the complex. Whereas the AP-1 factors are inducible, CREB and related proteins are constitutive and regulate gene transcription through phosphorylation. Due to seizure activity, many AP-1 factors are induced, but rapidly return to basal levels. However, if neuronal death occurs, fos-related antigens of 35 kDa persist for an extended period and may be involved in regulating genes related to neuronal plasticity. Similar factors are expressed after chronic drug treatment indicating a role in drug tolerance. However, during early CNS development, elevated AP-1 DNA binding consisting of c-jun and CREB occurs in every brain region and is inversely related to the degree of maturation of a particular brain area. These transcription factors are important for gene regulation during CNS dysfunction and development and those present specify which genes are activated.
转录因子是可改变基因表达的调节蛋白。任何需要改变mRNA水平的细胞功能都依赖于这些因子。中枢神经系统中，转录因子的激活蛋白1（AP-1；c-fos和fos相关抗原加上jun相关因子）家族以及环磷腺苷效应元件结合蛋白（CREB）家族已得到广泛研究。DNA结合复合物由AP-1和CREB因子之间形成的二聚体组成，结合特异性取决于构成该复合物的蛋白质。AP-1因子是可诱导的，而CREB及相关蛋白是组成型的，并通过磷酸化调节基因转录。由于癫痫发作活动，许多AP-1因子被诱导，但会迅速恢复到基础水平。然而，如果发生神经元死亡，35 kDa的fos相关抗原会持续较长时间，并可能参与调节与神经元可塑性相关的基因。慢性药物治疗后会表达类似的因子，表明其在药物耐受性中起作用。然而，在中枢神经系统早期发育过程中，由c-jun和CREB组成的AP-1 DNA结合在每个脑区都会升高，并且与特定脑区的成熟程度呈负相关。这些转录因子在中枢神经系统功能障碍和发育过程中的基因调节中很重要，它们决定了哪些基因被激活。
