PACE4 (PCSK6): another proprotein convertase link to iron homeostasis?
Open accessAbstract
We read with great interest the recent article by Pagani et al. Although the authors indicated that the cleavage occurs at the cell surface and is regulated by diferric transferrin, 1 they did not identify the sheddase involved in this process.
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The PCSK6 gene is involved in iron homeostasis and hence related with iron deficiency anemia.
“while the PCSK6 gene is involved in iron homeostasis and hence related with iron deficiency anemia (Guillemot and Seidah, 2015).”
From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as Guillemot and Seidah, 2015
The conclusion (p. 1) suggests that PACE4 (PCSK6) is implicated in iron homeostasis, possibly through TfR2 cleavage or BMP6 activation. It does not mention iron deficiency anemia or establish a relationship with that condition, and it presents PACE4’s role as a suggestion rather than a confirmed finding. (LLM, conf=0.88)
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Cites
Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis
Silvestri, L., Pagani, A., & Camaschella, C. (2008) · Blood · doi:10.1182/blood-2007-07-100677 · Cited by 311 · see citing works
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Research works printed but not linked: 8
- [2]Seidah NG, Prat A. The biology and therapeutic targeting of the proprotein convertases. Nat Rev Drug Discov. 2012;11(5):367-383.
- [3]Guillemot J, Canuel M, Essalmani R, Prat A, Seidah NG. Implication of the proprotein convertases in iron homeostasis: proprotein convertase 7 sheds human transferrin receptor 1 and furin activates hepcidin. Hepatology. 2013;57(6):2514-2524.
- [5]Essalmani R, Hamelin J, Marcinkiewicz J, et al. Deletion of the gene encoding proprotein convertase 5/6 causes early embryonic lethality in the mouse. Mol Cell Biol. 2006;26(1):354-361.
- [6]Fleming RE, Migas MC, Holden CC, et al. Transferrin receptor 2: continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis. Proc Natl Acad Sci USA. 2000; 97(5):2214-2219.
- [7]Essalmani R, Susan-Resiga D, Chamberland A, et al. Furin is the primary in vivo convertase of angiopoietin-like 3 and endothelial lipase in hepatocytes. J Biol Chem. 2013;288(37):26410-26418.
- [8]Nour N, Mayer G, Mort JS, et al. The Cysteine-rich Domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinases. Mol Biol Cell. 2005;16(11):5215-5226.
- [9]Camaschella C. BMP6 orchestrates iron metabolism. Nat Genet. 2009;41(4):386-388.
- [10]Yuasa K, Futamatsu G, Kawano T, et al. Subtilisin-like proprotein convertase paired basic amino acid-cleaving enzyme 4 is required for chondrogenic differentiation in ATDC5 cells. FEBS J. 2012; 279(21):3997-4009.
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Mekonnen, Y. A., Gültas, M., Effa, K., Hanotte, O., & Schmitt, A. O. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.01095 · Cited by 37 · see citing works
“doi: 10.1038/sj.gene.6364345 Kim, C. H., and Broxmeyer, H. E. (1999). Chemokines: signal lamps for trafficking of T and B cells for development and effector function.”
BackgroundInfluential
- Authors
- Guillemot, J., & Seidah, N. G.
- Affiliations
- Montreal Clinical Research Institute (CA)
- Venue
- Haematologica
- Published
- 2015-09-01
- Volume
- 100
- Issue
- 9
- Pages
- e377-e377
- ISSN
- 0390-6078 (ISSN-L)
- 1592-8721
- PMC
- PMC4800706
- OpenAlex
- W1865125576
- Cited by
- 6
- References
- 1
- Citations by year
- 2023: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2017: 1 · 2015: 1
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Haematologica (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- PCSK6, PACE4, proprotein convertases, iron homeostasis, diferric transferrin, sheddases
- MeSH terms
- Cell Membrane, Humans, Iron, Receptors, Transferrin
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