RUNX3与p53：两种肿瘤抑制因子如何协同对抗致癌性Ras？

RUNX3 and p53: How Two Tumor Suppressors Cooperate Against Oncogenic Ras?

作者信息

Lee Jung-Won, van Wijnen Andre, Bae Suk-Chul

机构信息

Department of Biochemistry, School of Medicine, and Institute for Tumor Research, Chungbuk National University, Cheongju, 28644, South Korea.

Departments of Orthopedic Surgery & Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

出版信息

Adv Exp Med Biol. 2017;962:321-332. doi: 10.1007/978-981-10-3233-2_20.

DOI:10.1007/978-981-10-3233-2_20

PMID:28299666

Abstract

RUNX family members play pivotal roles in both normal development and neoplasia. In particular, RUNX1 and RUNX2 are essential for determination of the hematopoietic and osteogenic lineages, respectively. RUNX3 is involved in lineage determination of various types of epithelial cells. Analysis of mouse models and human cancer specimens revealed that RUNX3 acts as a tumor suppressor via multiple mechanisms. p53-related pathways play central roles in tumor suppression through the DNA damage response and oncogene surveillance, and RUNX3 is involved in both processes. In response to DNA damage, RUNX3 facilitates p53 phosphorylation by the ATM/ATR pathway and p53 acetylation by p300. When oncogenes are activated, RUNX3 induces ARF, thereby stabilizing p53. Here, we summarize the molecular mechanisms underlying the p53-mediated tumor-suppressor activity of RUNX3.

摘要

RUNX家族成员在正常发育和肿瘤形成过程中都发挥着关键作用。特别是，RUNX1和RUNX2分别对造血谱系和骨生成谱系的确定至关重要。RUNX3参与多种类型上皮细胞的谱系确定。对小鼠模型和人类癌症标本的分析表明，RUNX3通过多种机制发挥肿瘤抑制作用。p53相关通路在通过DNA损伤反应和癌基因监测进行的肿瘤抑制中起核心作用，而RUNX3参与这两个过程。响应DNA损伤时，RUNX3通过ATM/ATR途径促进p53磷酸化，并通过p300促进p53乙酰化。当癌基因被激活时，RUNX3诱导ARF，从而稳定p53。在此，我们总结了RUNX3的p53介导的肿瘤抑制活性的分子机制。