Runx2 Protein Stabilizes Hypoxia-inducible Factor-1α through Competition with von Hippel-Lindau Protein (pVHL) and Stimulates Angiogenesis in Growth Plate Hypertrophic Chondrocytes

Lee, Sun Hee; Che, Xiangguo; Jeong, Jong Hwa; Choi, Je‐Yong; Lee, Young‐Joo; Lee, Jun Young; Bae, Suk‐Chul; Lee, You Mie

doi:10.1074/jbc.m112.340232

Cited by 90 publications

(64 citation statements)

References 43 publications

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“…However, how Runx2 downregulates IKKb is an open question. Given that Runx2 is a transcription factor, we can speculate that Runx2 promotes the expression of IKKb-degrading proteins such as Keap1 or that it acts as a repressor of the IKKb gene 32 .…”

Section: Naa10 Negatively Regulates Bone Development In Micementioning

confidence: 99%

NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2

et al. 2014

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Runt-related transcription factor 2 (Runx2) transactivates many genes required for osteoblast differentiation. The role of N-a-acetyltransferase 10 (NAA10, arrest-defective-1), originally identified in yeast, remains poorly understood in mammals. Here we report a new NAA10 function in Runx2-mediated osteogenesis. Runx2 stabilizes NAA10 in osteoblasts during BMP-2-induced differentiation, and NAA10 in turn controls this differentiation by inhibiting Runx2. NAA10 delays bone healing in a rat calvarial defect model and bone development in neonatal mice. Mechanistically, NAA10 acetylates Runx2 at Lys225, and this acetylation inhibits Runx2-driven transcription by interfering with CBFb binding to Runx2. Our study suggests that NAA10 acts as a guard ensuring balanced osteogenesis by fine-tuning Runx2 signalling in a feedback manner. NAA10 inhibition could be considered a potential strategy for facilitating bone formation.

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Section: Naa10 Negatively Regulates Bone Development In Micementioning

confidence: 99%

NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2

et al. 2014

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“…Following hydroxylation, HIF1␣ is ubiquitinated by the E3 ubiquitin ligase von Hippel-Lindau tumor suppressor and degraded via the proteasome pathway. Under hypoxia, prolyl hydroxylases are inactive due to lack of substrate, and HIF1␣ is no longer subjected to hydroxylation and degradation and can then bind to ARNT and activate transcription of HIF target genes (17)(18)(19).…”

mentioning

confidence: 99%

Hypoxia-inducible Factor 1α Regulates a SOCS3-STAT3-Adiponectin Signal Transduction Pathway in Adipocytes

Jiang

Kim

et al. 2013

Journal of Biological Chemistry

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Background: HIF1␣ in adipose tissue was induced during the pathogenesis of type 2 diabetes. Results: The HIF1␣ inhibitor acriflavine increased the expression of adiponectin through decreased expression of the novel HIF1␣ target gene Socs3 and transcriptional activation of Stat3 in vivo and in vitro. Conclusion: HIF1␣ regulates an adipocyte SOCS3-STAT3-adiponectin signal transduction pathway. Significance: Inhibitors of HIF1␣ provide a potential therapeutic target for the treatment of type 2 diabetes.

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“…MiR-204 is involved in the activation of the nuclear factor of activated T cell (NFAT) pathway, the Rho pathway, VSMC proliferation and resistance to apoptosis, as well as downregulation of transcripts such as bone morphogenetic protein receptor type II (BMPR2) and interleukin-6 (IL-6) [60][61][62]. Also, miR-204 regulates the expression of the Runt-related transcription factor 2 (RUNX2), which has been shown to stabilise HIF-1α in chondrocytes by competing with VHL [20,63]. In the context of hypoxia, RUNX2 is upregulated, since miR-204 is downregulated, and therefore sustains HIF-1α activation, which in turn contributes to aberrant VSMC proliferation, resistance to apoptosis and their transdiferentiation to osteoblast-like cells [20].…”

Section: Role Of Hypoxia-inducible Micrornas In Pulmonary Hypertensionmentioning

confidence: 99%

Hypoxia and Pulmonary Hypertension

Charolidi¹,

Carroll²

2017

Hypoxia and Human Diseases

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Vasoconstriction in response to low oxygen tension (hypoxia) in pulmonary arteries is an important physiological adaptation to reroute blood low to areas of higher oxygenation for efective gaseous exchange. However, chronic hypoxia is a common feature of lung disease, such as chronic obstructive pulmonary disease (COPD). Hypoxic stress triggers cellular phenotypic alterations including increased proliferation and migration of vascular smooth muscle cells (VSMCs), as well as synthesis of extracellular matrix (ECM) proteins that remodel lung vasculature. Remodelling of vessels increases the risk of pulmonary hypertension (PH)-elevated pulmonary arterial pressure-and eventually right heart failure. This chapter will summarise the major pathways and mechanisms involved in hypoxia-driven pulmonary hypertension (PH).

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Runx2 Protein Stabilizes Hypoxia-inducible Factor-1α through Competition with von Hippel-Lindau Protein (pVHL) and Stimulates Angiogenesis in Growth Plate Hypertrophic Chondrocytes

Cited by 90 publications

References 43 publications

NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2

NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2

Hypoxia-inducible Factor 1α Regulates a SOCS3-STAT3-Adiponectin Signal Transduction Pathway in Adipocytes

Hypoxia and Pulmonary Hypertension

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