The Role of Proprotein Convertases in the Regulation of the Function of Immune Cells in the Oncoimmune Response

Rose, Mélanie; Duhamel, Marie; Rodet, Franck; Salzet, Michel

doi:10.3389/fimmu.2021.667850

Cited by 18 publications

(11 citation statements)

References 63 publications

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“…In this review, our discussions focus on the role of PCSK6 in cardiovascular biology. More information on PCSK6 and cancers can be found in several comprehensive reviews [ 27 , 28 , 29 ].…”

Section: Pcsk6 Gene and Tissue Expressionmentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease

Chen

2022

IJMS

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Proprotein convertase subtilisin/kexin 6 (PCSK6) is a secreted serine protease expressed in most major organs, where it cleaves a wide range of growth factors, signaling molecules, peptide hormones, proteolytic enzymes, and adhesion proteins. Studies in Pcsk6-deficient mice have demonstrated the importance of Pcsk6 in embryonic development, body axis specification, ovarian function, and extracellular matrix remodeling in articular cartilage. In the cardiovascular system, PCSK6 acts as a key modulator in heart formation, lipoprotein metabolism, body fluid homeostasis, cardiac repair, and vascular remodeling. To date, dysregulated PCSK6 expression or function has been implicated in major cardiovascular diseases, including atrial septal defects, hypertension, atherosclerosis, myocardial infarction, and cardiac aging. In this review, we describe biochemical characteristics and posttranslational modifications of PCSK6. Moreover, we discuss the role of PCSK6 and related molecular mechanisms in cardiovascular biology and disease.

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“…In this review, our discussions focus on the role of PCSK6 in cardiovascular biology. More information on PCSK6 and cancers can be found in several comprehensive reviews [ 27 , 28 , 29 ].…”

Section: Pcsk6 Gene and Tissue Expressionmentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease

Chen

2022

IJMS

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“…Fuirn exists in two forms: a membrane-bound and a circulating soluble form secreted by the cells; the higher levels of the latter increases the risk of metabolic syndrome, diabetes and hypertension [77]. This enzyme, ubiquitously expressed in tissues, is a member of Ca +2 -dependent prohormone/proprotein convertase (PC) family involved in the proteolytic maturation of many hormones, neuropeptides, immune system molecular effectors, growth factors, von Willebrand factor, receptors (like Notch receptors) and other enzymes such as ADAM17 (see below) and metalloproteinases (MMPs) [78][79][80][81][82]. Furin proteolytic modification of its substrates occurs through cleavage at the C-terminal end of multibasic motifs (Arg-X-Arg/Lys/Arg-Arg↓ homologous to RRAR residues at S1/S2 boundary; see S protein in above) in the substrates in the presence of Ca +2 [83].…”

Section: Furin a Ubiquitously Expressed Multifunctional Proteasementioning

confidence: 99%

S protein, ACE2 and Host Cell Proteases in SARS-CoV2 Cell Entry and Infectivity; Is Soluble ACE2 a Two Blade Sword?

Nejat¹,

Torshizi²,

Najafi³

2022

Preprint

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Since the spread of the deadly virus SARS-CoV2 in late 2019, researchers have restlessly been seeking for unraveling how the virus factually enters the host cells. Some proteins on each side of the interaction between the virus and the host cells are involved as the major contributors to this process: 1- the nano-machine Spike protein on behalf of the virus, 2- angiotensin converting enzyme II, the mono-carboxypeptidase and the key component of renin angiotensin system on behalf of the host cell, 3- some host proteases and proteins exploited by SARS-CoV2, In this review, the complex process of SARS-CoV2 entrance into the host cells with the contribution of the involved host proteins as well as the sequential conformational changes in the Spike protein tending to increase the probability of complexification of the latter with angiotensin converting enzyme II, the receptor of the virus on the host cells, are discussed. Besides, the release of the catalytic ectodomain of angiotensin converting enzyme II as its soluble form in the extracellular space and its positive or negative impact on the infectivity of the virus are considered.

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“…Nine PC subtilisin/kexin genes (PCSK1 to PCSK9) encoding for PC1/3, PC2, Furin, PC4, PC5/6, PACE4, PC7, SKI-1/S1P, and PCSK9 are known. The expression of PC1/3, PC2, PC5/6, Furin, and PC7 in lymphoid organs such as lymph nodes, thymus, and spleen has been found to play a role in these enzymes regarding immunity [ 14 ]. Proprotein convertases are in the group of proteases that cleave proteins and turn them into their active or inactive form.…”

Section: Cancer Hallmarks and Pcmentioning

confidence: 99%

“…Furthermore, Furin, via its proteolytic activity, manages the suppressive functions of Tregs and thus prevents chronic inflammation and autoimmune diseases. In other cells, such as macrophages, Furin mediates in the modulation of their inflammatory phenotype (M1) and has an important role in the defense against tumors [ 14 ]. Subsequently, Furin mediates in the activation control of macrophages.…”

Section: Furin and Tumor Immune Escapementioning

confidence: 99%

What Are the Roles of Proprotein Convertases in the Immune Escape of Tumors?

et al. 2022

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Protein convertases (PCs) play a significant role in post-translational procedures by transforming inactive precursor proteins into their active forms. The role of PCs is crucial for cellular homeostasis because they are involved in cell signaling. They have also been described in many diseases such as Alzheimer’s and cancer. Cancer cells are secretory cells that send signals to the tumor microenvironment (TME), remodeling the surrounding space for their own benefits. One of the most important components of the TME is the immune system of the tumor. In this review, we describe recent discoveries that link PCs to the immune escape of tumors. Among PCs, many findings have determined the role of Furin (PC3) as a paramount enzyme causing the TME to induce tumor immune evasion. The overexpression of various cytokines and proteins, for instance, IL10 and TGF-B, moves the TME towards the presence of Tregs and, consequently, immune tolerance. Furthermore, Furin is implicated in the regulation of macrophage activity that contributes to the increased impairment of DCs (dendritic cells) and T effector cells. Moreover, Furin interferes in the MHC Class_1 proteolytic cleavage in the trans-Golgi network. In tumors, the T cytotoxic lymphocytes (CTLs) response is impeded by the PD1 receptor (PD1-R) located on CTLs and its ligand, PDL1, located on cancer cells. The inhibition of Furin is a subtle means of enhancing the antitumor response by repressing PD-1 expression in tumors or macrophage cells. The impacts of other PCs in tumor immune escape have not yet been clarified to the extent that Furin has. Accordingly, the influence of other types of PCs in tumor immune escape is a promising topic for further consideration.

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The Role of Proprotein Convertases in the Regulation of the Function of Immune Cells in the Oncoimmune Response

Cited by 18 publications

References 63 publications

Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease

Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease

S protein, ACE2 and Host Cell Proteases in SARS-CoV2 Cell Entry and Infectivity; Is Soluble ACE2 a Two Blade Sword?

What Are the Roles of Proprotein Convertases in the Immune Escape of Tumors?

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