Institute for Genetic Medicine, Hokkaido University, Hokkaido 060-0815, Japan.
Cells. 2019 Jan 31;8(2):108. doi: 10.3390/cells8020108.
Leucine Rich Repeat of Flightless-1 Interacting Protein 1/GC-binding factor 2 (LRRFIP1/GCF2) cDNA was cloned for a transcriptional repressor GCF2, which bound sequence-specifically to a GC-rich element of epidermal growth factor receptor (EGFR) gene and repressed its promotor. LRRFIP1/GCF2 was also cloned as a double stranded RNA (dsRNA)-binding protein to trans-activation responsive region (TAR) RNA of Human Immunodeficiency Virus-1 (HIV-1), termed as TAR RNA interacting protein (TRIP), and as a binding protein to the Leucine Rich Repeat (LRR) of Flightless-1(Fli-1), termed as Flightless-1 LRR associated protein 1 (FLAP1) and LRR domain of Flightless-1 interacting Protein 1 (LRRFIP1). Subsequent functional studies have revealed that LRRFIP1/GCF2 played multiple roles in the regulation of diverse biological systems and processes, such as in immune response to microorganisms and auto-immunity, remodeling of cytoskeletal system, signal transduction pathways, and transcriptional regulations of genes. Dysregulations of LRRFIP1/GCF2 have been implicated in the causes of several experimental and clinico-pathological states and the responses to them, such as autoimmune diseases, excitotoxicity after stroke, thrombosis formation, inflammation and obesity, the wound healing process, and in cancers. LRRFIP1/GCF2 is a bioregulator in multidisciplinary systems of the human body and its dysregulation can cause diverse human diseases.
LRRFIP1/GC 结合因子 2（LRRFIP1/GCF2）的亮氨酸重复富含 Flightless-1 相互作用蛋白 1 cDNA 被克隆为转录抑制剂 GCF2，它特异性结合表皮生长因子受体（EGFR）基因的富含 GC 元件并抑制其启动子。LRRFIP1/GCF2 也被克隆为双链 RNA（dsRNA）结合蛋白，与人类免疫缺陷病毒 1（HIV-1）的转录激活反应元件（TAR）RNA 结合，称为 TAR RNA 相互作用蛋白（TRIP），以及与 Flightless-1（Fli-1）的亮氨酸丰富重复（LRR）结合的蛋白，称为 Flightless-1 LRR 相关蛋白 1（FLAP1）和 Flightless-1 相互作用蛋白 1 的 LRR 域（LRRFIP1）。随后的功能研究表明，LRRFIP1/GCF2 在调节多种生物系统和过程中发挥着多种作用，如对微生物和自身免疫的免疫反应、细胞骨架系统的重塑、信号转导途径以及基因的转录调控。LRRFIP1/GCF2 的失调与几种实验和临床病理状态及其反应有关，如自身免疫性疾病、中风后兴奋毒性、血栓形成、炎症和肥胖、伤口愈合过程以及癌症。LRRFIP1/GCF2 是人体多学科系统中的生物调节剂，其失调可导致多种人类疾病。
