title: Posttranslational modifications of RUNX1 as potential anticancer targets.
abstract: The transcription factor RUNX1 is a master regulator of hematopoiesis. Disruption of RUNX1 activity has been implicated in the development of hematopoietic neoplasms. Recent studies also highlight the importance of RUNX1 in solid tumors both as a tumor promoter and a suppressor. Given its central role in cancer development, RUNX1 is an excellent candidate for targeted therapy. A potential strategy to target RUNX1 is through modulation of its posttranslational modifications (PTMs). Numerous studies have shown that RUNX1 activity is regulated by PTMs, including phosphorylation, acetylation, methylation and ubiquitination. These PTMs regulate RUNX1 activity either positively or negatively by altering RUNX1-mediated transcription, promoting protein degradation and affecting protein interactions. In this review, we first summarize the available data on the context- and dosage-dependent roles of RUNX1 in various types of neoplasms. We then provide a comprehensive overview of RUNX1 PTMs from biochemical and biologic perspectives. Finally, we discuss how aberrant PTMs of RUNX1 might contribute to tumorigenesis and also strategies to develop anticancer therapies targeting RUNX1 PTMs.
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: S
authors.initials: S
authors.lastname: Goyama
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: G
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kurokawa
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Mulloy
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000235:genetics; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy / Q000379:methods*; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000235:genetics; D014443:Tyrosine / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human; D014443:Tyrosine; D008239:Lysine