ongogene:Myc驱动的淋巴瘤中p53调节转录的全基因组分析

2017-01-24 MedSci MedSci原创

肿瘤抑制基因p53是控制细胞应激反应的转录因子。近期,一项发表在Oncogene杂志上的文章详细分析了基于p53基因组和基因调控在Myc驱动的淋巴瘤中恢复p53触发的转录程序。在启动子和增强子处鉴定出p53结合位点,两者的特征在于存在活性染色质标记。这些位点中只有一小部分显示20个碱基对p53共有基序,表明募集p53到基因组DNA上主要是通过染色质中蛋白质 - 蛋白质相互作用介导的。 p53也靶向

肿瘤抑制基因p53是控制细胞应激反应的转录因子。

近期,一项发表在Oncogene杂志上的文章详细分析了基于p53基因组和基因调控在Myc驱动的淋巴瘤中恢复p53触发的转录程序。

在启动子和增强子处鉴定出p53结合位点,两者的特征在于存在活性染色质标记。这些位点中只有一小部分显示20个碱基对p53共有基序,表明募集p53到基因组DNA上主要是通过染色质中蛋白质 - 蛋白质相互作用介导的。 p53也靶向激活远端位点但缺乏激活标记物,这是通过序列识别驱动。

在所有情况下,相关基序是规范的非分裂共有元件,没有明确证据表明p53募集是通过分裂基序完成的。

在启动子中,p53绑定到共识基序与基因诱导有关,但不是抑制,表明后者最可能是间接的。

总之,这些数据表明p53基因组识别的关键特征,并提供前所未有的与p53重新激活和肿瘤退化相关的路径,铺平了他们在治疗中的应用。

原始出处:
Tonelli C, Morelli MJ, Sabò A, et al.Genome-wide analysis of p53-regulated transcription in Myc-driven lymphomas.Oncogene. 2017 Jan 16. doi: 10.1038/onc.2016.443.

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    2017-11-22 mjldent
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    2017-02-18 cy0324
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    2017-01-26 guihongzh
  6. [GetPortalCommentsPageByObjectIdResponse(id=1736140, encodeId=50b11e36140fe, content=<a href='/topic/show?id=e5504182238' target=_blank style='color:#2F92EE;'>#基因组分析#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41822, encryptionId=e5504182238, topicName=基因组分析)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3e5234086891, createdName=xue8613, createdTime=Sat Sep 09 08:07:00 CST 2017, time=2017-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1747222, encodeId=b7871e472222b, content=<a href='/topic/show?id=832e93345c3' target=_blank style='color:#2F92EE;'>#转录#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93345, encryptionId=832e93345c3, topicName=转录)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=58df35929710, createdName=mjldent, createdTime=Wed Nov 22 22:07:00 CST 2017, time=2017-11-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2048762, encodeId=3aab2048e6202, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Sat Feb 18 14:07:00 CST 2017, time=2017-02-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1719799, encodeId=501f1e1979964, content=<a href='/topic/show?id=d57a29400ba' target=_blank style='color:#2F92EE;'>#全基因组分析#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29400, encryptionId=d57a29400ba, topicName=全基因组分析)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4b0b32824865, createdName=yangshch, createdTime=Thu Jul 20 19:07:00 CST 2017, time=2017-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1274798, encodeId=ac9112e4798bd, content=<a href='/topic/show?id=1bbc12404ba' target=_blank style='color:#2F92EE;'>#MYC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12404, encryptionId=1bbc12404ba, topicName=MYC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=66ec123, createdName=guihongzh, createdTime=Thu Jan 26 04:07:00 CST 2017, time=2017-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372369, encodeId=522513e2369b5, content=<a href='/topic/show?id=9d861362e53' target=_blank style='color:#2F92EE;'>#p53#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13627, encryptionId=9d861362e53, topicName=p53)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5d70341, createdName=zhishijing, createdTime=Thu Jan 26 04:07:00 CST 2017, time=2017-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1546462, encodeId=8d5c154646285, content=<a href='/topic/show?id=81eb2939373' target=_blank style='color:#2F92EE;'>#全基因组#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29393, encryptionId=81eb2939373, topicName=全基因组)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dc2113925052, createdName=ms1692810954239974, createdTime=Thu Jan 26 04:07:00 CST 2017, time=2017-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=172425, encodeId=9c531e242552, content=很好的学习资料, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20170207/IMG589913E36908D4741.jpg, createdBy=99331680071, createdName=knowheart, createdTime=Tue Jan 24 22:48:10 CST 2017, time=2017-01-24, status=1, ipAttribution=)]
    2017-01-26 zhishijing
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    2017-01-24 knowheart

    很好的学习资料

    0

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近日,发表在国际杂志Science上的一篇研究论文中,来自麻省理工学院等处的研究人员通过研究发现,蛋白p53或可通过免疫球蛋白死亡结构域1α (DD1α)来进行细胞凋亡机制的控制。 有机体为了存活,就会不断产生新的机体细胞来替代老化死亡的细胞,同时死亡细胞会持续性地被收集并且被移除体外;当机体的净化系统一旦“迷路”就会使得机体将死亡细胞视为外来入侵物,并且对其进行攻击最终引发多种类型的免疫疾

盘点:肿瘤干细胞——星星之火 可以燎原

肿瘤干细胞 表观遗传 乳腺癌 大肠癌 p53 西兰花 双重装备促使纳米颗粒精准狙杀癌症干细 中国科学家发现肝癌干细胞自我更新调控新机制胞 姜黄素抑制肝癌干细胞生长 肝癌治疗新提示 趋化因子受体CCR7促进乳腺癌肿瘤干细胞生长

CDD:激活p53的小分子MMRi化合物可能成为癌症潜在药物

最近,美国Roswell Park癌症研究所(RPCI)药理学和治疗学系的一个研究团队,发现了一类新的小分子化合物,是为白血病和淋巴瘤开发新的靶向疗法的很好候选对象。这类新的化合物可迫使癌细胞自杀,研究人员将这项研究结果发表在了Cell Death and Disease杂志。 该研究的资深作者Xinjiang Wang博士表示:“我们对这些化合物的独特活性感到非常兴奋,并将继续专注于我们的研究

Nature:肿瘤抑制蛋白竟驱动恶性癌症

近日,来自宾夕法尼亚大学等处的科学家通过研究发现,恶性肿瘤的生长及DNA序列未发生改变的基因活性的变化往往和突变的p53蛋白质直接相关,相关研究结果刊登于国际著名杂志Nature上,该研究或为开发应对难以治疗的癌症的新型策略提供帮助。 TP53是所有人类癌症中频繁突变的基因,其可以编码一种名为p53的肿瘤抑制蛋白,p53通常会通过调节细胞分裂的循环来抑制肿瘤,而p53蛋白也会通过维持细胞快速

ASCO 2016:靶向p53的抗癌药物APR-246临床试验取得成功

英国利物浦大学领导的一项药物临床试验旨在开发新的癌症治疗方法。这项临床试验取得的较好结果已在两个美国医学会议上发布。这项药物临床试验旨在测试一种新的化合物(APR-246)对一种特定蛋白(p53)的影响,其中p53在所有癌症的至少一半中发生突变。p53基因属于一类被称作肿瘤抑制基因的基因。在所有高分级浆液性卵巢癌(serous ovarian cancer)病例中,肿瘤抑制基因发生突变,但是在

盘点:肿瘤抑制因子p53亮点研究一览

p53是迄今为止细胞中最为重要的肿瘤抑制因子之一,人类50%以上的肿瘤细胞中都发现有它的缺失或突变。近年来发现:p53在细胞代谢,尤其在葡萄糖代谢中也起着重要作用。 近年来就有研究者就发现机体中肿瘤抑制蛋白p53的新功能,当机体由于压力因素致使健康细胞DNA损伤时,这种蛋白就会首先出来保护DNA,例如当机体暴露在有毒化学物质或强烈的太阳紫外线下时,如果损伤非常严重,p53就会启动细胞死亡或细