ArticleThe Journal of biological chemistry2013
Proprotein convertase subtilisin/kexin type 7 (PCSK7) is essential for the zebrafish development and bioavailability of transforming growth factor β1a (TGFβ1a).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Sex Disparity in Systemic Sclerosis-Associated Pulmonary Fibrosis.International journal of molecular sciences · 2026Article
- Evaluating the causal effects of circulating plasma proteins on the risk of malignant neoplasms of bone and articular cartilage.The Journal of international medical research · 2026Article
- The Biology and Clinical Implications of PCSK7.Endocrine reviews · 2025Review
- PCSK7, a potential target for the treatment of age-related macular degeneration: inhibition of retinal epithelial cell death.International journal of clinical and experimental pathology · 2024Article
- FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes.International journal of molecular sciences · 2021Review
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- The motif EThe Journal of biological chemistry · 2020Article
- Article
- Intelectin 3 is dispensable for resistance against a mycobacterial infection in zebrafish (Danio rerio).Scientific reports · 2019Article
- Article
- The proprotein convertase subtilisin/kexin furinA regulates zebrafish host response against Mycobacterium marinum.Infection and immunity · 2015Article
- Proprotein convertase FURIN constrains Th2 differentiation and is critical for host resistance against Toxoplasma gondii.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
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Authors and funding
10 authors.
Funding
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Abstract
Proprotein convertase subtilisin/kexin (PCSK) enzymes convert proproteins into bioactive end products. Although other PCSK enzymes are known to be essential for biological processes ranging from cholesterol metabolism to host defense, the in vivo importance of the evolutionarily ancient PCSK7 has remained enigmatic. Here, we quantified the expressions of all pcsk genes during the 1st week of fish development and in several tissues. pcsk7 expression was ubiquitous and evident already during the early development. To compare mammalian and zebrafish PCSK7, we prepared homology models, which demonstrated remarkable structural conservation. When the PCSK7 function in developing larvae was inhibited, we found that PCSK7-deficient fish have defects in various organs, including the brain, eye, and otic vesicle, and these result in mortality within 7 days postfertilization. A genome-wide analysis of PCSK7-dependent gene expression showed that, in addition to developmental processes, several immune system-related pathways are also regulated by PCSK7. Specifically, the PCSK7 contributed to the mRNA expression and proteolytic cleavage of the cytokine TGFβ1a. Consequently, tgfβ1a morphant fish displayed phenotypical similarities with pcsk7 morphants, underscoring the importance of this cytokine in the zebrafish development. Targeting PCSK activity has emerged as a strategy for treating human diseases. Our results suggest that inhibiting PCSK7 might interfere with normal vertebrate development.
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