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Notch1
名称: Notch1
描述:
Notch基因发现于1916年,其突变可造成果蝇的残翅, 20世纪80年代中期Artavanis Tsakonas研究组首次克隆了该基因。Notch基因编码的单链跨膜受体蛋白分子量约300 kD,由2753个氨基酸残基组成。研究发现, Notch从无脊椎动物到脊椎动物的多个物种中均表达, 其家族成员的结构具有高度保守性,在细胞分化、发育中起着关键作用。Notch信号介入多种细胞的凋亡、增殖、和细胞分化多效性作用,调节多细胞动物的形态发育和形成。Notch信号通路是一个既简单又复杂的信号通路，在多个物种中表达。Notch信号对于细胞的生长发育具有广泛的多样化的影响，包括干细胞的维持；细胞分化、增殖和凋亡的决定。许多体外及动物实验中已证实，活化的Notch可使正常细胞向恶性转化。已有越来越多的证据表明异常的Notch信号与一些人类肿瘤的发生发展相关。
The Notch gene belongs to a family of epidermal growth factor (EGF) like homeotic genes, which encode transmembrane proteins with a variable number of cysteine rich EGF like repeats in the extracellular region. Four notch genes have been described in mammals: Notch1, Notch2, Notch3 and Notch4 (Int3), which have been implicated in the differentiation of the nervous system and other structures. The EGF like proteins Delta and Serrate have been identified as ligands of Notch1. Mature Notch proteins are heterodimeric receptors derived from the cleavage of Notch pre-proteins into an extracellular subunit (NEC) containing multiple EGF like repeats and a transmembrane subunit including intracellular region (Ntm).
The Notch signaling pathway was first identified in Drosophila. The Notch 1 protein is a single pass transmembrane receptor activated through the Delta (Dl) and Serrate (Ser) ligands in Drosophila (and their mammalian counterparts Delta like 3 and Jagged 1 and 2). Activation results in the proteolytic cleavage of the cytoplasmic portion of Notch (120kDa) which localizes to the nucleus to interact with DNA binding proteins (RB Jk/KBF2/CBF1). The interaction of Notch with these proteins converts them from transcriptional repressors to activators, thus affecting the expression of a variety of target genes. During maturation, the Notch molecule is cleaved by furin-like convertase at the extracellular domain. Upon binding to a ligand such as Delta1, or upon extracellular calcium depletion, the C terminal Notch 1 fragment dissociates from its N terminal counterpart and is further cleaved between Gly1743 and Val1744. The resulting activated cytosolic fragment translocates to the nucleus and activates Notch related transcription
The Notch signaling pathway was first identified in Drosophila. The Notch 1 protein is a single pass transmembrane receptor activated through the Delta (Dl) and Serrate (Ser) ligands in Drosophila (and their mammalian counterparts Delta like 3 and Jagged 1 and 2). Activation results in the proteolytic cleavage of the cytoplasmic portion of Notch (120kDa) which localizes to the nucleus to interact with DNA binding proteins (RB Jk/KBF2/CBF1). The interaction of Notch with these proteins converts them from transcriptional repressors to activators, thus affecting the expression of a variety of target genes. During maturation, the Notch molecule is cleaved by furin-like convertase at the extracellular domain. Upon binding to a ligand such as Delta1, or upon extracellular calcium depletion, the C terminal Notch 1 fragment dissociates from its N terminal counterpart and is further cleaved between Gly1743 and Val1744. The resulting activated cytosolic fragment translocates to the nucleus and activates Notch related transcription
参考文献:
# Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation EMBO J. 2001 Jul 2;20(13):3427-36.
病毒转染实验是研究目的基因、目的蛋白功能极其有效的分子生物学方法，其原理是构建过表达或者iRNA干扰病毒质粒，根据实验需要，分别包装成腺病毒、慢病毒、逆转录病毒，感染宿主细胞或动物组织，调控宿主细胞或动物组织相应基因表达及蛋白合成，为了解目的基因及蛋白对细胞功能的调控提供了有利的手段，广泛受到科研工作者重视及青睐，成为分 子机制研究不可缺少的重要实验手段。
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