Furin as proprotein convertase and its role in normal and pathological biological processes

Solov'eva, N. I.; Ta, Gureeva; Timoshenko, O.S.; Moskvitina, T. A.; Кугаевская, Е. В.

doi:10.18097/pbmc20166206609

Cited by 9 publications

(3 citation statements)

References 127 publications

(187 reference statements)

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“…The large extracellular region of furin has an overall homology with the same region of other members of the PC family [1]. The signal peptide directs translocation of the ~ 104-kDa pro-enzyme into the endoplasmic reticulum (ER), where the first cleavage in the inhibitory prodomain takes place via autocatalytic cleavage by the catalytic domain [42][43][44]. The second cut in the prodomain is made during trafficking of the propeptide-furin complex within the mildly acidic trans-Golgi network/endosomal system, which yields the active ~ 81-kDa mature enzyme.…”

Section: Protein Structure and Expression Of Furinmentioning

confidence: 99%

The emerging role of furin in neurodegenerative and neuropsychiatric diseases

Zhang

Gao

Bai

et al. 2022

Transl Neurodegener

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Furin is an important mammalian proprotein convertase that catalyzes the proteolytic maturation of a variety of prohormones and proproteins in the secretory pathway. In the brain, the substrates of furin include the proproteins of growth factors, receptors and enzymes. Emerging evidence, such as reduced FURIN mRNA expression in the brains of Alzheimer’s disease patients or schizophrenia patients, has implicated a crucial role of furin in the pathophysiology of neurodegenerative and neuropsychiatric diseases. Currently, compared to cancer and infectious diseases, the aberrant expression of furin and its pharmaceutical potentials in neurological diseases remain poorly understood. In this article, we provide an overview on the physiological roles of furin and its substrates in the brain, summarize the deregulation of furin expression and its effects in neurodegenerative and neuropsychiatric disorders, and discuss the implications and current approaches that target furin for therapeutic interventions. This review may expedite future studies to clarify the molecular mechanisms of furin deregulation and involvement in the pathogenesis of neurodegenerative and neuropsychiatric diseases, and to develop new diagnosis and treatment strategies for these diseases.

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Section: Protein Structure and Expression Of Furinmentioning

confidence: 99%

The emerging role of furin in neurodegenerative and neuropsychiatric diseases

Zhang

Gao

Bai

et al. 2022

Transl Neurodegener

View full text Add to dashboard Cite

show abstract

“…This protein requires the activity of pathogens such as bacterial toxins, enveloped viruses such as the Human Immunodeficiency Virus (HIV), Ebola, and SARS-Cov-2. Certainly, it is also involved in increasing the pathogenicity of the virus because cutting the target site, activates the virus functionally [58]. in vitro studies have shown that suppression of furin can decrease viral infections [59].…”

Section: Furinmentioning

confidence: 99%

The role of proteases in the invasion of SARS-CoV-2 virus into human host cells

Saeidi

Rouhollah

2021

J Curr Biomed Rep

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The new coronavirus, which originally broke out in Wuhan, China, in December 2019, increase quickly around the world, causing a pandemic all over the world. The virus uses its spike protein to enter the human host cells. Protein S binds to the angiotensin-converting enzyme II (ACE2) receptor and enters the host cell. For the more successful binding, several proteases facilitate and optimize this binding, the most important of which are transmembrane protease serine 2 (TMPRSS2), furin, and cathepsin L proteases. After binding of protein S to the ACE2 receptor, cleavage of protein S is required for membrane fusion by protein S, which causes viral entry into host cells. This proteolytic activity may be cathepsin L-dependent and occurs with changes in pH in cell endosomes, or it may occur through serine proteases activity at the surface of the host cell membrane or within vesicles. Finally, the cell becomes infected with the virus. Several studies have tried to reduce the rate of viral infection by using inhibitors of these proteases.

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“…Furin, pro-protein convertase subtilisin/kexin family member 3, is a calcium-dependent protease and it is present in all mammalian cells [13]. Furin with the other six members (PC1/3, PC2, PACE 4, PC4, PC5/6, and PC7/8) constitute the pro-protein convertases family that is responsible for cleavage and activation of various protein precursors in cells [14,15].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of the pro‐protein convertase furin predicts prognosis and promotes papillary thyroid carcinoma progression and metastasis through RAF/MEK signaling

et al. 2023

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Furin belongs to the pro-protein convertases (PCs) family and its aberrant expression has been documented in various types of cancers; however, its role in thyroid cancer remains unclear. We investigated the expression of furin in a large cohort of Middle Eastern papillary thyroid carcinoma (PTC) patient samples and explored its functional role and mechanism in PTC cell lines in vitro and in vivo. Furin overexpression was observed in 44.6% of all PTC cases and was significantly associated with aggressive clinicopathological parameters and poor outcomes. We show that the knockdown of FURIN suppresses tumor growth, proliferation, migration, invasion, spheroid growth, and progression of epithelial-to-mesenchymal transition (EMT) in B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutant cells, whereas its overexpression in BRAF wild-type PTC cell lines reversed the effect. FURIN knockdown in the BRAF mutant cell line led to reduced tumor growth and increased apoptosis. Mechanistically, FURIN knockdown led to MEK/ERK pathway suppression in BRAF mutant cells, although inhibition of MEK did not affect furin expression, which suggests that furin acts through the MEK/ERK pathway. Furthermore, our study revealed the synergistic antitumor effect of furin depletion and anti-MEK inhibitor treatment. Overall, these results indicate that furin is an important prognostic marker in Middle Eastern PTC and that it plays a crucial role in BRAF-associated MAP/ERK pathway activation and tumorigenesis. Furin inhibition could be a potential therapeutic target for aggressive PTC.

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Furin as proprotein convertase and its role in normal and pathological biological processes

Cited by 9 publications

References 127 publications

The emerging role of furin in neurodegenerative and neuropsychiatric diseases

The emerging role of furin in neurodegenerative and neuropsychiatric diseases

The role of proteases in the invasion of SARS-CoV-2 virus into human host cells

Overexpression of the pro‐protein convertase furin predicts prognosis and promotes papillary thyroid carcinoma progression and metastasis through RAF/MEK signaling

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