PU.1 is a major transcriptional activator of the tumour suppressor gene LIMD1.

PU.1 is a major transcriptional activator of the tumour suppressor gene LIMD1.
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DOI:
10.1016/j.febslet.2011.03.013
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发表时间:
2011-04-06
期刊:
影响因子:
3.5
通讯作者:
Sharp TV
Sharp TV
中科院分区:
生物学3区
文献类型:
--
作者:
Foxler DE;James V;Shelton SJ;Vallim TQ;Shaw PE;Sharp TV

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LIMD 1是一种肿瘤抑制基因,在80%的肺癌∼中表达下调,在乳腺癌和头颈部鳞状细胞癌中也有表达缺失。LIMD1也是儿童急性淋巴细胞性白血病的候选TSG。在机制上,LIMD1与pRb相互作用,抑制E2F驱动的转录,同时也是microRNA介导的基因沉默的关键组成部分。在本研究中,我们发现LIMD1启动子内的CpG岛包含一个与转录因子PU.1保守的结合基序。PU.1共识的突变使启动子驱动的转录减少了90%。芯片和EMSA分析表明,PU1与LIMD1启动子特异性结合。PU.1的siRNA缺失显著降低了内源性LIMD1的表达,表明PU.1是LIMD1的主要转录激活因子。
LIMD1 is a tumour suppressor gene (TSG) down regulated in ∼80% of lung cancers with loss also demonstrated in breast and head and neck squamous cell carcinomas. LIMD1 is also a candidate TSG in childhood acute lymphoblastic leukaemia. Mechanistically, LIMD1 interacts with pRB, repressing E2F-driven transcription as well as being a critical component of microRNA-mediated gene silencing. In this study we show a CpG island within the LIMD1 promoter contains a conserved binding motif for the transcription factor PU.1. Mutation of the PU.1 consensus reduced promoter driven transcription by 90%. ChIP and EMSA analysis demonstrated that PU.1 specifically binds to the LIMD1 promoter. siRNA depletion of PU.1 significantly reduced endogenous LIMD1 expression, demonstrating that PU.1 is a major transcriptional activator of LIMD1.
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