ArticleThe Journal of biological chemistry2011
Inhibition of proprotein convertase SKI-1 blocks transcription of key extracellular matrix genes regulating osteoblastic mineralization.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
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- Transcription factor old astrocyte specifically induced substance is a novel regulator of kidney fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- FAM210A is a novel determinant of bone and muscle structure and strength.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Using Human 'Experiments of Nature' to Predict Drug Safety Issues: An Example with PCSK9 Inhibitors.Drug safety · 2018Article
- Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1.Nature communications · 2017Article
- Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus.Nature communications · 2017Article
- The PCSK9 revolution and the potential of PCSK9-based therapies to reduce LDL-cholesterol.Global cardiology science & practice · 2017Review
- Article
- Deletion of Mbtps1 (Pcsk8, S1p, Ski-1) Gene in Osteocytes Stimulates Soleus Muscle Regeneration and Increased Size and Contractile Force with Age.The Journal of biological chemistry · 2016Article
- MBTPS1/SKI-1/S1P proprotein convertase is required for ECM signaling and axial elongation during somitogenesis and vertebral development†.Human molecular genetics · 2015Article
- Type IV collagen is a novel DEJ biomarker that is reduced by radiotherapy.Journal of dental research · 2014Article
- Enamel organic matrix: potential structural role in enamel and relationship to residual basement membrane constituents at the dentin enamel junction.Connective tissue research · 2014Article
- Article
- In vitro differentiation and mineralization of dental pulp stem cells on enamel-like fluorapatite surfaces.Tissue engineering. Part C, Methods · 2012Article
- Escherichia coli cold-shock gene profiles in response to over-expression/deletion of CsdA, RNase R and PNPase and relevance to low-temperature RNA metabolism.Genes to cells : devoted to molecular & cellular mechanisms · 2012Article
- Osteocyte regulation of bone mineral: a little give and take.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2012Review
- The stimulation of adipose-derived stem cell differentiation and mineralization by ordered rod-like fluorapatite coatings.Biomaterials · 2012Article
- The biology and therapeutic targeting of the proprotein convertases.Nature reviews. Drug discovery · 2012Review
- Inhibin A enhances bone formation during distraction osteogenesis.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2012Article
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Mineralization, a characteristic phenotypic property of osteoblastic lineage cells, was blocked by 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) and decanoyl-Arg-Arg-Leu-Leu-chloromethyl ketone (dec-RRLL-cmk), inhibitors of SKI-1 (site 1; subtilisin kexin like-1) protease. Because SKI-1 is required for activation of SREBP and CREB (cAMP-response element-binding protein)/ATF family transcription factors, we tested the effect of these inhibitors on gene expression. AEBSF decreased expression of 140 genes by 1.5-3.0-fold including Phex, Dmp1, COL1A1, COL11A1, and fibronectin. Direct comparison of AEBSF and dec-RRLL-cmk, a more specific SKI-1 inhibitor, demonstrated that expression of Phex, Dmp1, COL11A1, and fibronectin was reduced by both, whereas COL1A2 and HMGCS1 were reduced only by AEBSF. AEBSF and dec-RRLL-cmk decreased the nuclear content of SKI-1-activated forms of transcription factors SREBP-1, SREBP-2, and OASIS. In contrast to AEBSF, the actions of dec-RRLL-cmk represent the sum of its direct actions on SKI-1 and indirect actions on caspase-3. Specifically, dec-RRLL-cmk reduced intracellular caspase-3 activity by blocking the formation of activated 19-kDa caspase-3. Conversely, overexpression of SKI-1-activated SREBP-1a and CREB-H in UMR106-01 osteoblastic cells increased the number of mineralized foci and altered their morphology to yield mineralization nodules, respectively. In summary, SKI-1 regulates the activation of transmembrane transcription factor precursors required for expression of key genes required for mineralization of osteoblastic cultures in vitro and bone formation in vivo. Our results indicate that the differentiated phenotype of osteoblastic cells and possibly osteocytes depends upon the non-apoptotic actions of SKI-1.
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