Subtilisin‐like proprotein convertase paired basic amino acid‐cleaving enzyme 4 is required for chondrogenic differentiation in <scp>ATDC</scp>5 cells

Yuasa, Keizo; Futamatsu, Go; Kawano, Tsuyoshi; Muroshita, Masaki; Kageyama, Yoko; Taichi, Hiromi; Ishikawa, Hiroshi; Nagahama, Masami; Matsuda, Yoshiko; Tsuji, Akihiko

doi:10.1111/j.1742-4658.2012.08758.x

Cited by 10 publications

(6 citation statements)

References 40 publications

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“…Indeed, the latency lasso region in which these residues are localized appears fundamental for proper folding of the dimer (Figure ). Notably, at variance with other BMPs, BMP6 is secreted along with the prodomain, which is eventually cleaved in the extracellular matrix by a convertase (PACE4) associated with heparan sulfate proteoglycans . The BMP6 prodomain by itself appears to have an important role in facilitating a proper interaction with the extracellular matrix and the subsequent cleavage into the functionally mature peptide, suggesting the potential pathogenicity of other amino acid substitutions not primarily affecting the protein secretion.…”

Section: Discussionmentioning

confidence: 99%

Identification of new BMP6 pro‐peptide mutations in patients with iron overload

et al. 2017

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Hereditary Hemochromatosis (HH) is a genetically heterogeneous disorder caused by mutations in at least five different genes (HFE, HJV, TFR2, SLC40A1, HAMP) involved in the production or activity of the liver hormone hepcidin, a key regulator of systemic iron homeostasis. Nevertheless, patients with an HH-like phenotype that remains completely/partially unexplained despite extensive sequencing of known genes are not infrequently seen at referral centers, suggesting a role of still unknown genetic factors. A compelling candidate is Bone Morphogenetic Protein 6 (BMP6), which acts as a major activator of the BMP-SMAD signaling pathway, ultimately leading to the upregulation of hepcidin gene transcription. A recent seminal study by French authors has described three heterozygous missense mutations in BMP6 associated with mild to moderate lateonset iron overload (IO). Using an updated next-generation sequencing (NGS)-based genetic test in IO patients negative for the classical HFE p.Cys282Tyr mutation, we found three BMP6 heterozygous missense mutations in four patients from three different families. One mutation (p. Leu96Pro) has already been described and proven to be functional. The other two (p.Glu112Gln, p.Arg257His) were novel, and both were located in the pro-peptide domain known to be crucial for appropriate BMP6 processing and secretion. In silico modeling also showed results consistent with their pathogenetic role. The patients' clinical phenotypes were similar to that of other patients with BMP6-related IO recently described. Our results independently add further evidence to the role of BMP6 mutations as likely contributing factors to late-onset moderate IO unrelated to mutations in the established five HH genes.

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Section: Discussionmentioning

confidence: 99%

Identification of new BMP6 pro‐peptide mutations in patients with iron overload

et al. 2017

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“…На сегодняшний день хорошо изучены ферменты, ответственные за внутриклеточный процессинг ПОМК из семейства сериновых протеиназ субтилизин/кексинового типа [51]. У млекопитающих известны семь пропротеиновых конвертаз (РС), осуществляющих посттрансляционный процессинг ПОМК и его производных: PC1 (также известная как PC3 и SPC3subtilisin-like proprotein convertase), PC2/SPC2, фурин (SPC1), PACE4 (paired basic amino acid cleaving enzyme)/SPC4, PC4/SPC5, PC5 (синонимы: PC6 и SPC6) и PC7 (синонимы: SPC7, LPC или PC8) [60]. Сохранение каталитических доменов и их вариабельность предполагает, что гены PC эволюционируют из общего гена-предшественника.…”

Section: биосинтезunclassified

Регуляторные Пептиды Семейства Меланокортинов: Биосинтез, Рецепция, Биологические Эффекты

Dodonova¹,

Белых²,

Бобынцев³

2018

Курск. науч.-практ. вестн. «Человек и его здоровье»

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В обзоре выполнен анализ данных литературы о биосинтезе, рецепции, деградации и физиологических эффектах регуляторных пептидов семейства меланокортинов. Представлены данные о взаимодействии меланокортинов с нейромедиаторами головного мозга, а также их влиянии на функциональное состояние регуляторных систем организма. Отражены нейротропные и иммунотропные эффекты пептидов семейства меланокортинов, а также их влияние на отдельные органы и системы, в частности: печень, сердечно-сосудистую систему и гемостаз. Описаны основные фармакологические эффекты и механизмы действия созданного на основе синтетического фрагмента АКТГ препарата «Семакс». Приведенные в обзоре данные отражают обоснованные значительным количеством исследований представления о высокой физиологической активности и полифункциональности регуляторных пептидов семейства меланокортинов, а также перспективность создания на их основе новых фармакологических препаратов.

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“…Quantitative real-time PCR was conducted using ABI Prism 7000 Sequence Detection System (Applied Biosystems) with Power SYBR Green PCR Master Mix (Applied Biosystems) as previously described. 15) The following specific primers were used: tyrosinase, forward 5′-GTCGTCACCCTGAAAATCC-TAACT-3′ and reverse 5′-CATCGCATAAAACCT-GATGGC-3′; MITF, forward 5′-GTATGAACACGCA CTCTCGA-3′ and reverse 5′-GTAACGTATTTGC-CATTTGC-3′; and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), forward 5′-GTGTCCGTCGT GGATCTGA-3′ and reverse 5′-CCTGCTTCAC-CACCTTCTTG-3′. GAPDH was used as an internal control.…”

Section: Cell Viability Assaymentioning

confidence: 99%

Alisol B, a triterpene fromAlismatis rhizoma(dried rhizome ofAlisma orientale), inhibits melanin production in murine B16 melanoma cells

Yoshida

Ito

Matsuda

et al. 2017

Bioscience, Biotechnology, and Biochemistry

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To develop new whitening agents from natural products, we screened 80 compounds derived from crude drugs in Kampo medicine in a melanin synthesis inhibition assay using murine B16 melanoma cells. The screen revealed that treatment with alisol B, a triterpene from Alismatis rhizoma, significantly decreased both melanin content and cellular tyrosinase activity in B16 cells. However, alisol B did not directly inhibit mushroom tyrosinase activity in vitro. Therefore, we investigated the mechanism underlying the inhibitory effect of alisol B on melanogenesis. Alisol B suppressed mRNA induction of tyrosinase and its transcription factor, microphthalmia-associated transcription factor (MITF). Furthermore, alisol B reduced the phosphorylation of CREB and maintained the activation of ERK1/2. These results suggest that the reduction in melanin production by alisol B is due to the downregulation of MITF through the suppression of CREB and activation of ERK and that alisol B may be useful as a new whitening agent.

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Subtilisin‐like proprotein convertase paired basic amino acid‐cleaving enzyme 4 is required for chondrogenic differentiation in ATDC5 cells

Abstract: Keywords bone morphogenetic protein 6 (BMP6); chondrogenic differentiation; paired basic amino acid-cleaving enzyme 4 (PACE4); processing; subtilisin-like proprotein convertase (SPC)

Cited by 10 publications

References 40 publications

Identification of new BMP6 pro‐peptide mutations in patients with iron overload

Identification of new BMP6 pro‐peptide mutations in patients with iron overload

Регуляторные Пептиды Семейства Меланокортинов: Биосинтез, Рецепция, Биологические Эффекты

Alisol B, a triterpene fromAlismatis rhizoma(dried rhizome ofAlisma orientale), inhibits melanin production in murine B16 melanoma cells

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