Backbone Resonance Assignment of a Proteolysis-Resistant Fragment in the Oxygen-Dependent Degradation Domain of the Hypoxia Inducible Factor 1α

Kim, Do Hyoung; Lee, Si Hyung; Chi, Seung‐Wook; Nam, Ki Hoon; Han, Kyou‐Hoon

doi:10.1007/s10059-009-0065-4

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…However, the physiologically expressed HIF-1α is degraded by the body within minutes under normoxic conditions. It was found that the mechanism by which HIF-1α is rapidly degraded by the organism under normoxic conditions is the HIF-1α subunit functional region (CDS region) encoding 826 amino acids, which has an oxygen-dependent degradation structural domain (ODD) consisting of more than 200 amino acids, Hydroxylation of the 402nd and 564th proline residues in the ODD of the HIF-1α molecule catalyzed by proline hydroxylase (oxygen is required for this hydroxylation process), and the hydroxylated HIF-1α is rapidly degraded by ubiquitin protease (Jin et al, 2009;Kim et al, 2009;Wei et al, 2010). In contrast, under hypoxic conditions, because proline 402, 564 cannot be hydroxylated, HIF-1α accumulates and is transferred to the nucleus, where it activates the hypoxia-responsive gene cluster.…”

Section: Discussionmentioning

confidence: 99%

BMSC-Exosomes Carry Mutant HIF-1α for Improving Angiogenesis and Osteogenesis in Critical-Sized Calvarial Defects

Ying

Wang

et al. 2020

Front. Bioeng. Biotechnol.

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Repair and reconstruction of critical-sized bone defects has always been a difficult task in orthopedics. Hypoxia inducible factor-1α (HIF-1α) plays an important role in bone defect repair, it has the dual function of promoting osteogenesis and vascular regeneration, but it is quickly degraded by the body under normoxic conditions. Previously we prepared mutant HIF-1α, which has been shown to efficiently maintain cellular expression under normoxic conditions. In this study, we evaluated for the first time the role of exosomes of rat bone marrow mesenchymal stem cell carry mutant HIF-1α (BMSC-Exos-HIF1α) in repairing critical-sized bone defects. Evaluation of the effects of BMSC-Exos-HIF1α on bone marrow mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation by cell proliferation assay, alkaline phosphatase activity assay, alizarin red staining, real-time quantitative polymerase chain reaction. BMSC-Exos-HIF1α was loaded onto the β-TCP stent implanted in the bone defect area using a rat cranial critical-sized bone defect model, and new bone formation and neovascularization were detected in vivo by micro-CT, fluorescence labeling analysis, Microfil perfusion, histology and immunohistochemical analysis. In vitro results showed that BMSC-Exos-HIF1α stimulated the proliferation of BMSCs and upregulated the expression level of bone-related genes, which was superior to bone marrow MSC exosomes (BMSC-Exos). In vivo results showed that BMSC-Exos-HIF1α combined with β-TCP scaffold promoted new bone regeneration and neovascularization in the bone defect area, and the effect was better than that of BMSC-Exos combined with β-TCP scaffold. In this study, the results showed that BMSC-Exos-HIF1α stimulated the proliferation and osteogenic differentiation of BMSCs and that BMSC-Exos-HIF1α combined with β-TCP scaffolds could repair critical-sized bone defects by promoting new bone regeneration and neovascularization.

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Section: Discussionmentioning

confidence: 99%

BMSC-Exosomes Carry Mutant HIF-1α for Improving Angiogenesis and Osteogenesis in Critical-Sized Calvarial Defects

Ying

Wang

et al. 2020

Front. Bioeng. Biotechnol.

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“…NMR spectroscopy is a powerful tool that provides detailed structural characteristics of partially folded proteins or intrinsically unstructured/unfolded proteins (IUPs) at the amino acid residue level (Chi et al, 2005;Kim et al, 2009;Lee et al, 2000;2012). IUPs are peculiar proteins that are affiliated with a variety of biological functions including transcription, translation, and A B cell signaling as well as critical diseases such as prion diseases, amyloidgenesis, cancers, and viral infections but do not form unique three-dimensional structures under non-denaturing conditions (Chouard, 2011;Lee et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Structural Characterization of an Intrinsically Unfolded Mini-HBX Protein from Hepatitis B Virus

Lee

Cha

Lim

et al. 2012

Molecules and Cells

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The hepatitis B virus x protein (HBX) is expressed in HBVinfected liver cells and can interact with a wide range of cellular proteins. In order to understand such promiscuous behavior of HBX we expressed a truncated mini-HBX protein (named Tr-HBX) (residues 18-142) with 5 Cys Ser → mutations and characterized its structural features using circular dichroism (CD) spectropolarimetry, NMR spectroscopy as well as bioinformatics tools for predicting disorder in intrinsically unstructured proteins (IUPs). The secondary structural content of Tr-HBX from CD data suggests that Tr-HBX is only partially folded. The protein disorder prediction by IUPred reveals that the unstructured region encompasses its N-terminal ~30 residues of Tr-HBX. A two-dimensional 1 H-15 N HSQC NMR spectrum exhibits fewer number of resonances than expected, suggesting that Tr-HBX is a hybrid type IUP where its folded Cterminal half coexists with a disordered N-terminal region. Many IUPs are known to be capable of having promiscuous interactions with a multitude of target proteins. Therefore the intrinsically disordered nature of Tr-HBX revealed in this study provides a partial structural basis for the promiscuous structure-function behavior of HBX.

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Construction of adenovirus vector harboring RANTES regulated by oxygen-dependent degradation domain and its chemoattractant activity <I>in vitro</I>

Li¹,

Wu²,

Li³

et al. 2009

Acad J sec Mil Med Univ

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Backbone Resonance Assignment of a Proteolysis-Resistant Fragment in the Oxygen-Dependent Degradation Domain of the Hypoxia Inducible Factor 1α

Cited by 3 publications

References 23 publications

BMSC-Exosomes Carry Mutant HIF-1α for Improving Angiogenesis and Osteogenesis in Critical-Sized Calvarial Defects

BMSC-Exosomes Carry Mutant HIF-1α for Improving Angiogenesis and Osteogenesis in Critical-Sized Calvarial Defects

Structural Characterization of an Intrinsically Unfolded Mini-HBX Protein from Hepatitis B Virus

Construction of adenovirus vector harboring RANTES regulated by oxygen-dependent degradation domain and its chemoattractant activity <I>in vitro</I>

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