Phosphorylation, acetylation and ubiquitination: the molecular basis of RUNX regulation.
The RUNX family members play pivotal roles in normal development and neoplasia. RUNX1 and RUNX2 are essential for hematopoiesis and osteogenesis, respectively, while RUNX3 is involved in neurogenesis, thymopoiesis and functions as a tumor suppressor. Inappropriate levels of RUNX activity are associated with leukemia, autoimmune disease, cleidocranial dysplasia, craniosynostosis and various solid tumors. Therefore, RUNX activity must be tightly regulated to prevent tumorigenesis and maintain normal cell differentiation. Recent work indicates that RUNX activity is controlled by various extracellular signaling pathways, and that phosphorylation, acetylation and ubiquitination are important post-translational modifications of RUNX that affect its stability and activity. Defining the precise roles, these modifications that play in the regulation of RUNX function may reveal not only how the RUNX proteins are regulated but also how they are assembled into other regulatory machineries.
Bae
Suk-Chul
SC
Department of Biochemistry, College of Medicine and Institute for Tumor Research, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea. scbae@chungbuk.ac.kr
Lee
Yong Hee
YH
D000215:Acylation; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism; D001848:Bone Diseases, Developmental / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D050657:Core Binding Factor alpha Subunits / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D009417:Nerve Tissue / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism
D050657:Core Binding Factor alpha Subunits; D025801:Ubiquitin