The secret identities of TMPRSS2: Fertility factor, virus trafficker, inflammation moderator, prostate protector and tumor suppressor

Epstein, Richard J.

doi:10.3233/tub-211502

Cited by 12 publications

(8 citation statements)

References 152 publications

(193 reference statements)

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“…Mutagenetic studies have demonstrated that SRCR, but not LDLRA, plays an essential role in proteolytic activity of PD TMP . Therefore, it might be a debatable issue whether PD TMP after dissociation from the stem region retains its proteolytic function or gains a yet unraveled distinct activity [ 111 ]. It is worth reminding that Ca 2+ binding to or unbinding from a distinct domain of a protein determines the task the domain should fulfil [ 112 ] or affects the structural stabilization of the proteinases and substrates affinity [ 113 , 114 ].…”

Section: Tmprss2 Its Soluble Protease Domain and Calciummentioning

confidence: 99%

S Protein, ACE2 and Host Cell Proteases in SARS-CoV-2 Cell Entry and Infectivity; Is Soluble ACE2 a Two Blade Sword? A Narrative Review

2023

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Since the spread of the deadly virus SARS-CoV-2 in late 2019, researchers have restlessly sought to unravel how the virus 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-CoV-2. In this review, the complex process of SARS-CoV-2 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. Moreover, 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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Section: Tmprss2 Its Soluble Protease Domain and Calciummentioning

confidence: 99%

S Protein, ACE2 and Host Cell Proteases in SARS-CoV-2 Cell Entry and Infectivity; Is Soluble ACE2 a Two Blade Sword? A Narrative Review

2023

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“…Mutagenetic studies have demonstrated that SRCR, but not LDLRA, plays an essential role in proteolytic activity of PDTMP. Therefore, it has been debated whether PDTMP after dissociation from the stem region retains its proteolytic function or gains a yet unraveled distinct activity [105]. It is worth reminding that Ca +2 binding to or unbinding from a distinct domain of a protein determines the task the domain should fulfil [106] or affects the structural stabilization of the proteinases and substrates affinity [107,108].…”

Section: Tmprss2 Its Soluble Protease Domain and Calciummentioning

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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“…Transmembrane protease serine 2 (TMPRSS2) is a cell membrane protease that is highly expressed in epithelial cells of the nose, lung, colon, gallbladder, kidney, and prostate, and plays key roles in tissue homeostasis. − TMPRSS2 has a transmembrane domain, a linker region, and a canonical serine protease domain with both proteolytic and signal transduction activity. − TMPRSS2 can cleave after the peptide sequence QAR. , Aberrant expression of TMPRSS2 in cancer cells suggests it may be used as a diagnostic biomarker and possibly as a therapeutic target. , Some coronaviruses and influenza viruses are also dependent on TMPRSS2 for viral activation and cell entry. − TMPRSS2 inhibitors can reduce prostate cancer cell invasion and metastasis and partially prevent the entry of SARS-CoV-2 into the lung epithelial cells. − Monitoring TMPRSS2 activity has attracted broad attention due to its important value in imaging cancer cells, viral infection, and identification of inhibitors, − which has led to the development of fluorogenic peptide substrates and immunofluorescence antibodies. − TMPRSS2 selective imaging and accurate TMPRSS2 inhibitor screening may improve the diagnosis and treatment of cancer as well as COVID-19 and other emerging viruses.…”

Section: Introductionmentioning

confidence: 99%

Protease-Responsive Potential-Tunable AIEgens for Cell Selective Imaging of TMPRSS2 and Accurate Inhibitor Screening

et al. 2023

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Transmembrane protease serine 2 (TMPRSS2) is a plasma membrane protease that activates both spike protein of coronaviruses for cell entry and oncogenic signaling pathways for tumor progression. TMPRSS2 inhibition can reduce cancer invasion and metastasis and partially prevent the entry of SARS-CoV-2 into host cells. Thus, there is an urgent need for both TMPRSS2-selective imaging and precise screening of TMPRSS2 inhibitors. Here, we report a TMPRSS2-responsive surface-potential-tunable peptide-conjugated probe (EGTP) with aggregation-induced emission (AIE) features for TMPRSS2 selective imaging and accurate inhibitor screening. The amphiphilic EGTP was constructed with tunable surface potential and responsive efficiency with TMPRSS2 and its inhibitor. The rational construction of AIE luminogens (AIEgens) with modular peptides indicated that the cleavage of EGTP led to a gradual aggregation with bright fluorescence in high TMPRSS2-expressing cells. This strategy may have value for selective detection of cancer cells, SARS-CoV-2-target cells, and screening of protease inhibitors.

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The secret identities of TMPRSS2: Fertility factor, virus trafficker, inflammation moderator, prostate protector and tumor suppressor

Cited by 12 publications

References 152 publications

S Protein, ACE2 and Host Cell Proteases in SARS-CoV-2 Cell Entry and Infectivity; Is Soluble ACE2 a Two Blade Sword? A Narrative Review

S Protein, ACE2 and Host Cell Proteases in SARS-CoV-2 Cell Entry and Infectivity; Is Soluble ACE2 a Two Blade Sword? A Narrative Review

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

Protease-Responsive Potential-Tunable AIEgens for Cell Selective Imaging of TMPRSS2 and Accurate Inhibitor Screening

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