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公开(公告)号：US20050101769A1
公开(公告)日：2005-05-12
申请号：US10757745
申请日：2004-01-15
申请人： Stefan Pype , Jacques Remacle , Danny Huylebroeck
发明人： Stefan Pype , Jacques Remacle , Danny Huylebroeck
IPC分类号： G01N33/50 , A61K38/00 , A61K38/17 , A61P9/10 , A61P19/02 , A61P25/00 , A61P35/00 , A61P37/02 , A61P37/06 , A61P43/00 , C07K14/47 , C07K16/18 , C12N15/09 , C12N15/12 , C12Q1/68 , G01N33/15 , G01N33/566 , C07K14/705
CPC分类号： C07K14/4702 , A61K38/00
摘要： The present invention relates to novel proteins interacting with the cytoplasmic domain of CD40, which are useful in the treatment of CD40 and/or NF-KκB related diseases. Surprisingly, these proteins do not show significant homology with the TRAF-protein family and, therefore, offer the possibility to modulate the CD40 and/or NF-κB pathway independently from the TRAF-CD40 interaction.
摘要翻译： 本发明涉及与CD40的细胞质结构域相互作用的新型蛋白质，其可用于治疗CD40和/或NF-KkappaB相关疾病。 令人惊讶的是，这些蛋白质与TRAF蛋白家族没有显着的同源性，因此提供了独立于TRAF-CD40相互作用调节CD40和/或NF-κB途径的可能性。
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公开(公告)号：US20050272090A1
公开(公告)日：2005-12-08
申请号：US11196670
申请日：2005-08-03
IPC分类号： G01N33/50 , A61K39/395 , A61K45/00 , A61K48/00 , A61P35/04 , C07K14/435 , C07K14/47 , C12N15/09 , C12Q1/00 , C12Q1/02 , C12Q1/68 , G01N33/15 , C12N15/85
CPC分类号： C07K14/4702 , C12Q1/6897
摘要： A method of identifying transcription factors comprising providing cells with a nucleic acid sequence at least comprising a sequence CACCT (SEQ ID NO:1) as bait for the screening of a library encoding potential transcription factors and performing a specificity test to isolate said factors. Preferably, the bait comprises twice the CACCT (SEQ ID NO:1) sequence, more particularly the bait comprises one of the sequences CACCT-N-CACCT (a first SEQ ID NO:1 and a second SEQ ID NO:1 separated by N), CACCT-N-AGGTG (SEQ ID NO:1 and SEQ ID NO:3 separated by N), AGGTG-N-CACCT (SEQ ID NO:3 and SEQ ID NO:1 separated by N), or AGGTG-N-AGGTG (a first SEQ ID NO:3 and a second SEQ ID NO:3 separated by N), wherein N is a spacer sequence. The transcription factors identified using the methods of the invention include separated clusters of zinc fingers, such as, for example, a two-handed zinc finger transcription factor. Also, at least one such zinc finger transcription factor, denominated as SIP1, induces tumor metastasis by down regulation of the expression of E-cadherin. Compounds interfering with SIP1 activity can thus be used to prevent tumor invasion and metastasis.
摘要翻译： 鉴定转录因子的方法，包括向细胞提供至少包含序列CACCT（SEQ ID NO：1）的核酸序列作为诱饵，用于筛选编码潜在转录因子的文库并进行特异性测试以分离所述因子。 优选地，诱饵包含CACCT（SEQ ID NO：1）序列的两倍，更特别地，诱饵包含序列CACCT-N-CACCT（第一SEQ ID NO：1和由N分开的第二SEQ ID NO：1） ），CACCT-N-AGGTG（由N分离的SEQ ID NO：1和SEQ ID NO：3），AGGTG-N-CACCT（由N分离的SEQ ID NO：3和SEQ ID NO：1）或AGGTG-N -AGGTG（由N分开的第一个SEQ ID NO：3和第二个SEQ ID NO：3），其中N是间隔序列。 使用本发明的方法鉴定的转录因子包括分离的锌指簇，例如双指锌指转录因子。 此外，称为SIP1的至少一种这样的锌指转录因子通过下调E-钙粘蛋白的表达而诱导肿瘤转移。 因此可以使用干扰SIP1活性的化合物来预防肿瘤侵袭和转移。
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公开(公告)号：US07435806B2
公开(公告)日：2008-10-14
申请号：US11196670
申请日：2005-08-03
IPC分类号： C07H21/04
CPC分类号： C07K14/4702 , C12Q1/6897
摘要： A method of identifying transcription factors comprising providing cells with a nucleic acid sequence at least comprising a sequence CACCT (SEQ ID NO:1) as bait for the screening of a library encoding potential transcription factors and performing a specificity test to isolate said factors. Preferably, the bait comprises twice the CACCT (SEQ ID NO:1) sequence, more particularly the bait comprises one of the sequences CACCT-N-CACCT (a first SEQ ID NO:1 and a second SEQ ID NO:1 separated by N), CACCT-N-AGGTG (SEQ ID NO:1 and SEQ ID NO:3 separated by N), AGGTG-N-CACCT (SEQ ID NO:3 and SEQ ID NO:1 separated by N), or AGGTG-N-AGGTG (a first SEQ ID NO:3 and a second SEQ ID NO:3 separated by N), wherein N is a spacer sequence. The transcription factors identified using the methods of the invention include separated clusters of zinc fingers, such as, for example, a two-handed zinc finger transcription factor. Also, at least one such zinc finger transcription factor, denominated as SIP1, induces tumor metastasis by down regulation of the expression of E-cadherin. Compounds interfering with SIP1 activity can thus be used to prevent tumor invasion and metastasis.
摘要翻译： 鉴定转录因子的方法，包括向细胞提供至少包含序列CACCT（SEQ ID NO：1）的核酸序列作为诱饵，用于筛选编码潜在转录因子的文库并进行特异性测试以分离所述因子。 优选地，诱饵包含CACCT（SEQ ID NO：1）序列的两倍，更特别地，诱饵包含序列CACCT-N-CACCT（第一SEQ ID NO：1和由N分开的第二SEQ ID NO：1） ），CACCT-N-AGGTG（由N分离的SEQ ID NO：1和SEQ ID NO：3），AGGTG-N-CACCT（由N分离的SEQ ID NO：3和SEQ ID NO：1）或AGGTG-N -AGGTG（由N分开的第一个SEQ ID NO：3和第二个SEQ ID NO：3），其中N是间隔序列。 使用本发明的方法鉴定的转录因子包括分离的锌指簇，例如双指锌指转录因子。 此外，称为SIP1的至少一种这样的锌指转录因子通过下调E-钙粘蛋白的表达而诱导肿瘤转移。 因此可以使用干扰SIP1活性的化合物来预防肿瘤侵袭和转移。
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公开(公告)号：US06884779B2
公开(公告)日：2005-04-26
申请号：US09964238
申请日：2001-09-26
IPC分类号： A01K67/027 , A61K31/70 , A61K31/711 , A61K38/00 , A61K38/17 , A61K48/00 , C07K14/46 , C07K14/71 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/12 , C12Q1/68 , G01N33/15 , G01N33/50 , G01N33/566 , C07K14/00
CPC分类号： C07K14/71 , A01K2217/05 , A61K38/00
摘要： The current invention concerns SMAD-interacting protein(s) obtainable by a two-hybrid screening assay whereby SMAD1 C-domain fused to GAL4 DNA-binding domain as “bait” and a cDNA library from mouse embryo as “prey” are used. Some characteristics of a specific SMAD-interacting protein (SIP1) of the family of zinc finger/homeodomain proteins including d-crystallin enhancer binding protein and/or Drosophila zfh-1 include an inability to interact with full-size XSMAD1 in yeast, SIP1CZF binds to E2 box sites, SIP1CZF binds to the Brachyury protein binding site and interferes with Brachyury-mediated transcription activation in cells and also interacts with the C-domain of SMAD 1, 2 and 5. The minimal length of the amino acid sequence necessary for binding with SMAD appears to be a 51 amino acid domain encompassing amino acids 166-216 of SEQ ID NO: 2 having the amino acid sequence as depicted in the one letter code: QHLGVGMEAPLLGFPTMNSNLSEVQKVLQIVDNTVSRQKMDCKTEDISKLK (SEQ ID NO: 21).
摘要翻译： 本发明涉及通过双杂交筛选试验获得的SMAD相互作用蛋白质，其中使用与GAL4 DNA结合结构域作为“诱饵”融合的SMAD1 C-结构域和来自小鼠胚胎的cDNA文库作为“猎物”。 包括d-晶状蛋白增强子结合蛋白和/或果蝇zfh-1的锌指/同源结构域蛋白家族的特异性SMAD相互作用蛋白（SIP1）的一些特征包括不能与酵母中的全尺寸XSMAD1相互作用， SUB> CZF 结合E2盒位点，SIP1CZF 结合Brachyury蛋白结合位点并干扰Brachyury介导的细胞转录活化，并且还与SMAD 1的C结构域相互作用 ，2和5.与SMAD结合所需的氨基酸序列的最小长度似乎是包含SEQ ID NO：2的氨基酸166-216的51个氨基酸结构域，其具有如一字母代码所示的氨基酸序列 ：QHLGVGMEAPLLGFPTMNSNLSEVQKVLQIVDNTVSRQKMDCKTEDISKLK（SEQ ID NO：21）。
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公开(公告)号：US06313280B1
公开(公告)日：2001-11-06
申请号：US09449285
申请日：1999-11-24
IPC分类号： C70H2104
CPC分类号： C07K14/71 , A01K2217/05 , A61K38/00
摘要： The current invention concerns SMAD interacting protein(s) obtainable by a two-hybrid screening assay whereby SMAD1 C-domain fused to GAL4 DNA-binding domain as bait and a cDNA library from mouse embryo as prey are used. Some characteristics of a specific SMAD interacting protein (SIP1) of the family of zinc finger/homeodomain proteins including &dgr;-crystallin enhancer binding protein and/or Drosophila zfh-1 include an inability to interact with full size XSMAD1 in yeast, SIP1czf binds to E2 box sites, SIP1czf binds to the Brachyury protein binding site and interferes with Brachyury-mediated transcription activation in cells and also interacts with C-domain of SMAD 1, 2 and 5. The minimal length of the amino acid sequence necessary for binding with SMAD appears to be a 51 amino acid domain encompassing amino acids 166-216 of SEQ ID NO 2 having the amino acid sequence as depicted in the one letter code: QHLGVGMEAPLLGFPTMNSNLSEVQKVLQIVDNTVSRQKMDCKTEDISKLK (SEQ ID NO. 21).
摘要翻译： 本发明涉及通过双杂交筛选试验获得的SMAD相互作用蛋白质，其中使用与GAL4 DNA结合结构域作为诱饵融合的SMAD1 C-结构域和使用小鼠胚胎作为牺牲品的cDNA文库。 包括δ-晶状体蛋白增强子结合蛋白和/或果蝇zfh-1的锌指/同源结构域蛋白家族的特异性SMAD相互作用蛋白（SIP1）的一些特征包括不能与酵母中的全尺寸XSMAD1相互作用，SIP1czf与E2结合 SIP1czf结合Brachyury蛋白结合位点并干扰细胞中Brachyury介导的转录激活，并与SMAD 1,2和5的C结构域相互作用。与SMAD结合所需的氨基酸序列的最短长度出现 为包含SEQ ID NO：2的氨基酸166-216的51个氨基酸结构域，其具有如下一个字母代码所示的氨基酸序列：QHLGVGMEAPLLGFPTMNSNLSEVQKVLQIVDNTVSRQKMDCKTEDISKLK（SEQ ID NO.21）。
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