High mobility group protein-1 (HMG-1) is a unique activator of p53
High mobility group protein-1 (HMG-1) is a unique activator of p53
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DOI：
10.1101/gad.12.4.462
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发表时间：
1998-02-15
影响因子：
10.5
通讯作者：
Prives, C
中科院分区：
文献类型：
--
作者：
Jayaraman, L;Moorthy, NC;Prives, C
P53蛋白与DNA的结合受其与共价和非共价修饰物相互作用的刺激。我们报告了从HeLa核提取液中鉴定出一种激活P53 DNA结合的因子。对该因子进行纯化，鉴定为高迁移率族蛋白HMG-1。HMG-1属于高度保守的染色质相关核蛋白家族，它能弯曲DNA，促进各种转录因子与其同源DNA序列的结合。我们证明了重组的HMG-1在体外增强了P53的DNA结合，并且HMG-1和P53在体外可以直接相互作用。出乎意料的是，HMG-1还刺激了P53 Delta 30与DNA的结合，P53 Delta 30是一种被认为具有结构性活性的蛋白质的羧基末端缺失形式，这表明HMG-1刺激P53的机制与其他已知的P53激活剂不同。最后，通过瞬时转染实验，我们发现HMG-1在体内可以增加P53和P53 Delta 30介导的反式激活。HMG-1促进高阶P53核蛋白结构的组装，这些数据以及HMG-1能够弯曲DNA的事实表明，HMG-1可能通过一种新的机制激活P53 DNA结合，涉及靶DNA的结构变化。
The binding of p53 protein to DNA is stimulated by its interaction with covalent as well as noncovalent modifiers. We report the identification of a factor from HeLa nuclear extracts that activates p53 DNA binding. This factor was purified to homogeneity and identified as the high mobility group protein, HMG-1. HMG-1 belongs to a family of highly conserved chromatin-associated nucleoproteins that bend DNA and facilitate the binding of various transcription factors to their cognate DNA sequences. We demonstrate that recombinant His-tagged HMG-1 enhances p53 DNA binding in vitro and also that HMG-1 and p53 can interact directly in vitro. Unexpectedly, HMG-1 also stimulates DNA binding by p53 Delta 30, a carboxy terminally deleted form of the protein that is considered to be constitutively active, suggesting that HMG-1 stimulates p53 by a mechanism that is distinct from other known activators of p53. Finally, using transient transfection assays we show that HMG-1 can increase p53 and p53 Delta 30-mediated transactivation in vivo. HMG-1 promotes the assembly of higher order p53 nucleoprotein structures, and these data, along with the fact that HMG-1 is capable of bending DNA, suggest that HMG-1 may activate p53 DNA binding by a novel mechanism involving a structural change in the target DNA.