title: RUNX3 and p53: How Two Tumor Suppressors Cooperate Against Oncogenic Ras?
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.
authors.affiliation: Department of Biochemistry, School of Medicine, and Institute for Tumor Research, Chungbuk National University, Cheongju, 28644, South Korea.
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Departments of Orthopedic Surgery & Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. vanwijnen.andre@mayo.edu.
authors.forename: Andre
authors.initials: A
authors.lastname: van Wijnen
authors.affiliation: Department of Biochemistry, School of Medicine, and Institute for Tumor Research, Chungbuk National University, Cheongju, 28644, South Korea. scbae@chungbuk.ac.kr.
authors.forename: Suk-Chul
authors.initials: SC
authors.lastname: Bae
mesh_terms: D000818:Animals; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53
keywords: ARF; DNA damage; Oncogene surveillance; RUNX; Tumor suppressor; p53