解锁p53反应要素:DNA形状是关键。

IF 2.6 Q3 ONCOLOGY

Molecular and Cellular Oncology Pub Date : 2021-04-22 eCollection Date: 2021-01-01 DOI:10.1080/23723556.2021.1905489

Marina Farkas, Steven McMahon

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引用次数: 2

摘要

为了识别基因组中的特定调控序列(即应答元件，REs)，肿瘤抑制蛋白53 kDa (p53)表现出剂量依赖的选择性。一般来说，与参与细胞死亡正向调节的靶基因相关的REs结合需要比与细胞存活相关的REs更高水平的p53。我们最近的发现为这一现象提供了一种机械的解释。具体来说，我们证明了RE DNA序列编码的DNA形状的细微差异，决定了两种生物化学上不同的DNA结合模式的利用，最终与不同的生物学结果相关。

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Unlocking p53 response elements: DNA shape is the key.

For recognition of specific regulatory sequences in the genome (i.e., response elements, REs), the tumor suppressor protein 53 kDa (p53) exhibits dose-dependent selectivity. In general, binding to REs linked to target genes involved in the positive regulation of cell death requires higher levels of p53 than those connected to cell survival. Our recent findings provide a mechanistic explanation for this phenomenon. Specifically, we demonstrate that subtle differences in DNA shape, encoded in RE DNA sequence, determine the utilization of two biochemically distinct DNA-binding modes, ultimately connected to different biological outcomes.

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来源期刊

Molecular and Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research

CiteScore

3.20

自引率

0.00%

发文量

期刊介绍： For a long time, solid neoplasms have been viewed as relatively homogeneous entities composed for the most part of malignant cells. It is now clear that tumors are highly heterogeneous structures that evolve in the context of intimate interactions between cancer cells and endothelial, stromal as well as immune cells. During the past few years, experimental and clinical oncologists have witnessed several conceptual transitions of this type. Molecular and Cellular Oncology (MCO) emerges within this conceptual framework as a high-profile forum for the publication of fundamental, translational and clinical research on cancer. The scope of MCO is broad. Submissions dealing with all aspects of oncogenesis, tumor progression and response to therapy will be welcome, irrespective of whether they focus on solid or hematological neoplasms. MCO has gathered leading scientists with expertise in multiple areas of cancer research and other fields of investigation to constitute a large, interdisciplinary, Editorial Board that will ensure the quality of articles accepted for publication. MCO will publish Original Research Articles, Brief Reports, Reviews, Short Reviews, Commentaries, Author Views (auto-commentaries) and Meeting Reports dealing with all aspects of cancer research.