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    Antibodies to ARF-p19
    3.
    发明授权
    Antibodies to ARF-p19 有权
    ARF-p19的抗体

    公开(公告)号：US06482929B1

    公开(公告)日：2002-11-19

    申请号：US09610833

    申请日：2000-07-06

    申请人： Charles J. Sherr ,  Dawn E. Quelle

    发明人： Charles J. Sherr ,  Dawn E. Quelle

    IPC分类号： C07K1600

    CPC分类号： C07K14/4703 ,  A01K2217/05 ,  A01K2217/075 ,  A61K38/00 ,  C07K2319/00

    摘要： The INK4A (MTS1, CDKN2) gene encodes a specific inhibitor (InK4a-p16) of the cyclin D-dependent kinases CDK4 and CDK6. InK4a-p16 can block these kinase from phosphorylating the retinoblastoma protein (pRb), preventing exit from the G1 phase of the cell cycle. Deletions and mutations involving the gene encoding InK4a-p16, INK4A, occur frequently in cancer cells, implying that INK4a-p16, like pRb, suppresses tumor formulation. However, a completely unrelated protein (ARF-p19) arises in major part from an alternative reading frame of the mouse INK4A gene. Expression of an ARF-p19 cDNA (SEQ ID NO:1) in rodent fibroblasts induces both G1 and G2 phase arrest.

    摘要翻译： INK4A（MTS1，CDKN2）基因编码细胞周期蛋白D-依赖性激酶CDK4和CDK6的特异性抑制剂（InK4a-p16）。 InK4a-p16可以阻断这些激酶磷酸化视网膜母细胞瘤蛋白（pRb），从而阻止细胞周期的G1期退出。 涉及编码InK4a-p16，INK4A的基因的缺失和突变频繁发生在癌细胞中，意味着像pRb一样的INK4a-p16抑制了肿瘤的制备。 然而，完全不相关的蛋白质（ARF-p19）主要来自小鼠INK4A基因的替代阅读框架。 ARF-p19 cDNA（SEQ ID NO：1）在啮齿动物成纤维细胞中的表达诱导G1期和G2期停滞。

    ARF-p19, a novel regulator of the mammalian cell cycle
    4.
    发明授权
    ARF-p19, a novel regulator of the mammalian cell cycle 有权
    ARF-p19，哺乳动物细胞周期的新型调节剂

    公开(公告)号：US06172194B2

    公开(公告)日：2001-01-09

    申请号：US09247154

    申请日：1999-02-09

    申请人： Charles J. Sherr ,  Dawn E. Quelle

    发明人： Charles J. Sherr ,  Dawn E. Quelle

    IPC分类号： C07K1400

    CPC分类号： C07K14/4703 ,  A01K2217/05 ,  A01K2217/075 ,  A61K38/00 ,  C07K2319/00

    摘要： The INK4A (MTS1, CDKN2) gene encodes a specific inhibitor (InK4a-p16) of the cyclin D-dependent kinases CDK4 and CDK6. InK4a-p16 can block these kinase from phosphorylating the retinoblastoma protein (pRb), preventing exit from the G1 phase of the cell cycle. Deletions and mutations involving the gene encoding InK4a-p16, INK4A, occur frequently in cancer cells, implying that INK4a-p16, like pRb, suppresses tumor formulation. However, a completely unrelated protein (ARF-p19) arises in major part from an alternative reading frame of the mouse INK4A gene. Expression of an ARF-p19 cDNA (SEQ ID NO:1) in rodent fibroblasts induces both G1 and G2 phase arrest.

    摘要翻译： INK4A（MTS1，CDKN2）基因编码细胞周期蛋白D-依赖性激酶CDK4和CDK6的特异性抑制剂（InK4a-p16）。 InK4a-p16可以阻断这些激酶磷酸化视网膜母细胞瘤蛋白（pRb），从而阻止细胞周期的G1期退出。 涉及编码InK4a-p16，INK4A的基因的缺失和突变频繁发生在癌细胞中，这意味着像pRb一样的INK4a-p16抑制肿瘤制剂。 然而，完全不相关的蛋白质（ARF-p19）主要来自小鼠INK4A基因的替代阅读框架。 ARF-p19 cDNA（SEQ ID NO：1）在啮齿动物成纤维细胞中的表达诱导G1期和G2期停滞。

    InK4c-p18 and InK4d-p19, inhibitors of cyclin-dependent kinases CDK4 and CDK6, and uses thereof
    6.
    发明授权
    InK4c-p18 and InK4d-p19, inhibitors of cyclin-dependent kinases CDK4 and CDK6, and uses thereof 失效
    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。

    Cyclin D binding factor, and uses thereof
    7.
    发明授权
    Cyclin D binding factor, and uses thereof 有权

    公开(公告)号：US06303772B1

    公开(公告)日：2001-10-16

    申请号：US09280590

    申请日：1999-03-29

    申请人： Charles J. Sherr ,  Hiroshi Hirai ,  Sara M. Bodner ,  Kazushi Inoue

    发明人： Charles J. Sherr ,  Hiroshi Hirai ,  Sara M. Bodner ,  Kazushi Inoue

    IPC分类号： C07K122

    CPC分类号： C07K14/4705 ,  A01K2217/05 ,  A01K2217/075 ,  C07K2319/00

    摘要： The invention discloses a direct interaction between D-type cyclins and a novel myb-like transcription factor, DMP1, which specifically interacts with cyclin D2. The present invention also provides evidence that D-type cyclins regulate gene expression in an RB-independent manner. Also included is DMP1, the transcription factor composed of a central DNA-binding domain containing three atypical myb repeats flanked by highly acidic segments located at its amino- and carboxyterminal ends. The invention includes amino acid sequences coding for DMP1, and DNA and RNA nucleotide sequences that encode the amino acid sequences. A use of DMP1 as a transcription factor is disclosed due to its specificity in binding to oligonucleotides containing the nonamer consensus sequence CCCG(G/T)ATGT. In this aspect of the invention, DMP1 when transfected into mammalian cells, activates the transcription of a reporter gene driven by a minimal promoter containing concatamerized DMP1 binding sites.

    Cyclin D binding factor, and uses thereof
    8.
    发明授权
    Cyclin D binding factor, and uses thereof 失效
    细胞周期蛋白D结合因子及其用途

    公开(公告)号：US06673902B2

    公开(公告)日：2004-01-06

    申请号：US09892398

    申请日：2001-06-27

    申请人： Charles J. Sherr ,  Hiroshi Hirai ,  Sara M. Bodner ,  Kazushi Inoue

    发明人： Charles J. Sherr ,  Hiroshi Hirai ,  Sara M. Bodner ,  Kazushi Inoue

    IPC分类号： C07K1600

    CPC分类号： C07K14/4705 ,  A01K2217/05 ,  A01K2217/075 ,  C07K2319/00

    摘要： The invention discloses a direct interaction between D-type cyclins and a novel myb-like transcription factor, DMP1, which specifically interacts with cyclin D2. The present invention also provides evidence that D-type cyclins regulate gene expression in an RB-independent manner. Also included is DMP1, the transcription factor composed of a central DNA-binding domain containing three atypical myb repeats flanked by highly acidic segments located at its amino- and carboxyterminal ends. The invention includes amino acid sequences coding for DMP1, and DNA and RNA nucleotide sequences that encode the amino acid sequences. A use of DMP1 as a transcription factor is disclosed due to its specificity in binding to oligonucleotides containing the nonamer consensus sequence CCCG(G/T)ATGT. In this aspect of the invention, DMP1 when transfected into mammalian cells, activates the transcription of a reporter gene driven by a minimal promoter containing concatamerized DMP1 binding sites.

    摘要翻译： 本发明公开了D型细胞周期蛋白与与细胞周期蛋白D2特异性相互作用的新型myb样转录因子DMP1之间的直接相互作用。 本发明还提供了D型细胞周期蛋白以不依赖RB的方式调节基因表达的证据。 还包括DMP1，转录因子由包含三个非典型myb重复的中心DNA结合结构域组成，其侧翼为位于其氨基末端和羧基末端的高度酸性的片段。 本发明包括编码DMP1的氨基酸序列，以及编码氨基酸序列的DNA和RNA核苷酸序列。 公开了DMP1作为转录因子的用途，因为它在与含有非标记共有序列CCCG（G / T）ATGT的寡核苷酸的结合中具有特异性。 在本发明的这个方面，当转染到哺乳动物细胞中时，DMP1激活由含有连接的DMP1结合位点的最小启动子驱动的报道基因的转录。

    ARF-P19, a novel regulator of the mammalian cell cycle
    10.
    发明授权
    ARF-P19, a novel regulator of the mammalian cell cycle 有权
    ARF-P19是哺乳动物细胞周期的新型调节剂

    公开(公告)号：US06407062B1

    公开(公告)日：2002-06-18

    申请号：US09480718

    申请日：2000-01-07

    申请人： Charles J. Sherr ,  Dawn Quelle ,  Martine F. Roussel ,  Frederique Zindy ,  Jason D. Weber

    发明人： Charles J. Sherr ,  Dawn Quelle ,  Martine F. Roussel ,  Frederique Zindy ,  Jason D. Weber

    IPC分类号： C07K1400

    CPC分类号： C07K14/4738 ,  A01K2217/05 ,  A01K2217/075 ,  A61K38/00 ,  A61K48/00 ,  C07K14/4703 ,  C07K2319/00

    摘要： The INK4A (MTS1, CDKN2) gene encodes a specific inhibitor (InK4a-p16) of the cyclin D-dependent kinases CDK4 and CDK6. InK4a-p16 can block these kinase from phosphorylating the retinoblastoma protein (pRb), preventing exit from the G1 phase of the cell cycle. Deletions and mutations involving the gene encoding InK4a-p16, INK4A, occur frequently in cancer cells, implying that INK4a-p16, like pRb, suppresses tumor formulation. However, a completely unrelated protein (ARF-p19) arises in major part from an alternative reading frame of the mouse INK4A gene. Expression of an ARF-p19 cDNA (SEQ ID NO:1) in rodent fibroblasts induces both G1 and G2 phase arrest. Economical reutilization of protein coding sequences in this manner is without precedent in mammalian genomes, and the unitary inheritance of INK4a-p16 and ARF-p19 may reflect a dual requirement for both proteins in cell cycle control.

    摘要翻译： INK4A（MTS1，CDKN2）基因编码细胞周期蛋白D-依赖性激酶CDK4和CDK6的特异性抑制剂（InK4a-p16）。 InK4a-p16可以阻断这些激酶磷酸化视网膜母细胞瘤蛋白（pRb），从而阻止细胞周期的G1期退出。 涉及编码InK4a-p16，INK4A的基因的缺失和突变频繁发生在癌细胞中，意味着像pRb一样的INK4a-p16抑制了肿瘤的制备。 然而，完全不相关的蛋白质（ARF-p19）主要来自小鼠INK4A基因的替代阅读框架。 ARF-p19 cDNA（SEQ ID NO：1）在啮齿动物成纤维细胞中的表达诱导G1期和G2期停滞。 蛋白质编码序列的经济再利用在哺乳动物基因组中是没有先例的，INK4a-p16和ARF-p19的单位遗传可能反映了细胞周期控制中两种蛋白质的双重要求。