RUNX2-modifying enzymes: therapeutic targets for bone diseases
김우진, 신혜림, 김봉수, 김현정, 류현모,
소속 상세정보
김우진 ( Kim Woo-Jin )
Seoul National University School of Dentistry Department of Molecular Genetics
신혜림 ( Shin Hye-Lim )
Seoul National University School of Dentistry Department of Molecular Genetics
김봉수 ( Kim Bong-Soo )
Seoul National University School of Dentistry Department of Molecular Genetics
김현정 ( Kim Hyun-Jung )
Seoul National University School of Dentistry Department of Molecular Genetics
류현모 ( Ryoo Hyun-Mo )
Seoul National University School of Dentistry Department of Molecular Genetics
Abstract
RUNX2 is a master transcription factor of osteoblast differentiation. RUNX2 expression in the bone and osteogenic front of a suture is crucial for cranial suture closure and membranous bone morphogenesis. In this manner, the regulation of RUNX2 is precisely controlled by multiple posttranslational modifications (PTMs) mediated by the stepwise recruitment of multiple enzymes. Genetic defects in RUNX2 itself or in its PTM regulatory pathways result in craniofacial malformations. Haploinsufficiency in RUNX2 causes cleidocranial dysplasia (CCD), which is characterized by open fontanelle and hypoplastic clavicles. In contrast, gain-of-function mutations in FGFRs, which are known upstream stimulating signals of RUNX2 activity, cause craniosynostosis (CS) characterized by premature suture obliteration. The identification of these PTM cascades could suggest suitable drug targets for RUNX2 regulation. In this review, we will focus on the mechanism of RUNX2 regulation mediated by PTMs, such as phosphorylation, prolyl isomerization, acetylation, and ubiquitination, and we will summarize the therapeutics associated with each PTM enzyme for the treatment of congenital cranial suture anomalies.
키워드
Acetylation; Osteoporosis
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