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US6033847A InK4c-p18 and InK4d-p19, inhibitors of cyclin-dependent kinases CDK4 and CDK6, and uses thereof 失效
标题翻译： InK4c-p18和InK4d-p19，细胞周期蛋白依赖性激酶CDK4和CDK6的抑制剂及其用途
公开(公告)号：US6033847A
公开(公告)日：2000-03-07
申请号：US384106
申请日：1995-02-06
申请人： Charles J. Sherr , James Downing , Hiroshi Hirai , Tsukasa Okuda
发明人： Charles J. Sherr , James Downing , Hiroshi Hirai , Tsukasa Okuda
IPC分类号： G01N33/53 , A61K31/70 , A61K48/00 , A61P35/00 , C07K14/47 , C07K14/52 , C07K16/24 , C12N15/09 , C12N15/12 , C12Q1/68 , G01N33/15 , G01N33/574 , C07H21/00 , C07K14/435 , C12N15/85
CPC分类号： C07K14/47 , A01K2217/05 , C07K2319/00
摘要： Members of the InK4 (Inhibitors of CDK4) family inhibit the activities of specific cyclin D-dependent kinases (CDK4 and/or CDK6), thereby arresting cell cycle progression in G1 phase and preventing chromosomal DNA replication. Disclosed herein are novel mammalian InK4 family members, having apparent molecular masses of 18,000 and 19,000 daltons, designated "InK4c-p18" and "InK4d-p19," respectively, or simply "p18" and "p19." In particular, the invention provides p19 genes and proteins isolated from murine or human cells and p18 genes and proteins from murine cells. When constitutively expressed in cells, p19 inhibits cyclin D-dependent kinase activity in vivo and induces G1 phase arrest. Materials and methods disclosed herein include (1) nucleic acids that encode p18 or p19; (2) methods for detecting nucleic acids encoding p18 or p19 proteins; (3) methods for producing p18 or p19 proteins using nucleic acids that encode p18 or p19, respectively; (4) purified pl8 or p19 proteins and peptide fragments, oligopeptides, or fusion proteins derived therefrom; (5) methods of inhibiting cells from replicating their chromosomal DNA using purified p18 or p19 proteins or derivatives thereof; (6) antibodies that specifically bind p18 or p19; (7) methods for detecting p18 and p19 proteins; (8) methods of stimulating cell growth by blocking p18 or p19 expression via antisense oligonucleotides; (9) methods of gene therapy using nucleic acids that encode p18 or p19; and (10) methods of making transgenic non-human animals that have alterations in the gene encoding p18 or p19, or in both genes.
摘要翻译： InK4（CDK4抑制剂）家族的成员抑制特异性细胞周期蛋白D依赖性激酶（CDK4和/或CDK6）的活性，从而阻止G1期的细胞周期进程并防止染色体DNA复制。本文公开了新颖的哺乳动物InK4家族成员，其分子量分别为18,000和19,000道尔顿，分别称为“InK4c-p18”和“InK4d-p19”，或简称为“p18”和“p19”。特别地，本发明提供从鼠或人细胞分离的p19基因和蛋白质，以及来自鼠细胞的p18基因和蛋白质。当细胞中组成型表达时，p19在体内抑制细胞周期蛋白D依赖性激酶活性，并诱导G1期停滞。本文公开的材料和方法包括（1）编码p18或p19的核酸; （2）检测编码p18或p19蛋白质的核酸的方法; （3）分别使用编码p18或p19的核酸产生p18或p19蛋白的方法; （4）纯化的p18或p19蛋白质和肽片段，寡肽或从其衍生的融合蛋白; （5）使用纯化的p18或p19蛋白或其衍生物抑制细胞复制染色体DNA的方法; （6）特异性结合p18或p19的抗体; （7）检测p18和p19蛋白的方法; （8）通过反义寡核苷酸阻断p18或p19表达刺激细胞生长的方法; （9）使用编码p18或p19的核酸进行基因治疗的方法; 和（10）制备在编码p18或p19的基因或两种基因中具有改变的转基因非人动物的方法。

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