Affinage

PRSS8

Prostasin · UniProt Q16651

Length
343 aa
Mass
36.4 kDa
Annotated
2026-06-10
34 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRSS8 (prostasin/CAP1) is a GPI-anchored epithelial serine protease that controls epithelial barrier integrity, sodium homeostasis, and inflammatory and oncogenic signaling, with many of its essential functions executed independently of its own catalytic activity (PMID:16061697, PMID:24706745, PMID:33650216). It is synthesized as a zymogen that co-localizes with the type II transmembrane serine protease matriptase across normal epithelia, and the two engage in a mutual cell-surface activation relationship in which prostasin is required for matriptase zymogen activation while genetically lying downstream of HAI-1/HAI-2-regulated matriptase (PMID:17471493, PMID:22952456). Dissection of separate catalytic-dead and zymogen-locked knockin alleles shows that prostasin's epidermal permeability barrier function requires neither its enzymatic activity nor activation-site cleavage, whereas hair follicle development requires its proteolytic activation by matriptase (PMID:24706745, PMID:26719335); loss of barrier function in epidermal knockouts causes fatal neonatal dehydration with defective corneocyte and tight-junction maturation (PMID:16061697). In skin, PRSS8 signals through PAR2 as a downstream effector, since PAR2 ablation rescues the hyperplasia, ichthyosis, and inflammation caused by epidermal CAP1/Prss8 overexpression (PMID:21245842). PRSS8 activates the epithelial sodium channel ENaC through a non-catalytic scaffold mechanism sufficient for baseline sodium balance, with proteolytic activation contributing additionally under ENaC inhibition, and it acts in part by regulating ENaC subunit protein abundance together with matriptase (PMID:22705055, PMID:33650216, PMID:37830556); renal prostasin further couples ENaC activity to aldosterone synthesis and the renin-angiotensin-aldosterone axis through a kidney-adrenal cross-talk that can be overridden by dietary potassium (PMID:35743186, PMID:40938892). In epithelial homeostasis and cancer, PRSS8 suppresses TLR4/NF-κB inflammatory signaling in the intestine in a microbiota-dependent manner (PMID:31916038) and restrains oncogenic Wnt/β-catenin and EMT programs, in part by promoting E-cadherin expression non-enzymatically (PMID:30115975, PMID:19849847). Its expression is silenced post-transcriptionally by m6A-dependent mRNA degradation via YTHDF2, with PRSS8 then lowering nuclear β-catenin through E-cadherin (PMID:38462165). PRSS8 also acts as a sheddase of the TGF-β co-receptor TGFBR3 to modulate TGF-β signaling (PMID:42184470).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2005 High

    Established that PRSS8 is essential for the epidermal permeability barrier, answering whether this protease has a non-redundant role in epithelial physiology.

    Evidence Skin-specific conditional knockout mouse with barrier, lipid, differentiation-marker, and tight-junction readouts

    PMID:16061697

    Open questions at the time
    • Did not determine whether the barrier role requires enzymatic activity
    • Molecular substrates underlying corneocyte and tight-junction defects unidentified
  2. 2007 Medium

    Placed PRSS8 in a cell-surface proteolytic cascade with matriptase, addressing how the prostasin zymogen becomes activated in epithelia.

    Evidence Enzymatic gene trapping and co-localization immunohistochemistry across epithelial tissues

    PMID:17471493

    Open questions at the time
    • Direct enzymatic activation assay not shown
    • Co-localization does not prove a direct activation event
  3. 2011 High

    Identified PAR2 as the downstream effector of PRSS8 signaling in skin, explaining how prostasin dysregulation drives hyperplasia and inflammation.

    Evidence K14-CAP1/Prss8 transgenic mice crossed into PAR2-null background with double-mutant rescue

    PMID:21245842

    Open questions at the time
    • Did not establish whether PAR2 cleavage is direct or proteolysis-dependent
    • Effector pathway downstream of PAR2 not dissected
  4. 2012 High

    Resolved the directionality of the matriptase-prostasin relationship, showing a mutual activation rather than a strictly linear cascade.

    Evidence Genetic epistasis of Prss8 hypomorphs with HAI-1/HAI-2 KO plus biochemical activation-state analysis in placenta

    PMID:22952456

    Open questions at the time
    • Mechanism of matriptase-independent prostasin activation unidentified
    • Generalizability beyond placental context not established
  5. 2012 High

    Demonstrated that PRSS8 stimulates ENaC activity and that natural CAP1/Prss8 mutations impair this, linking prostasin to sodium transport.

    Evidence In vitro ENaC activation assays with frizzy/hairless mutant proteins and in vivo amiloride-sensitive current in distal colon

    PMID:22705055

    Open questions at the time
    • Did not separate catalytic from non-catalytic contributions to ENaC activation
    • Molecular mechanism of ENaC stimulation undefined
  6. 2013 High

    Defined a tissue-specific requirement for PRSS8 in placental labyrinth maturation, explaining the embryonic lethality of constitutive loss.

    Evidence Constitutive versus epiblast-specific conditional knockout mice with histology

    PMID:23405214

    Open questions at the time
    • Molecular targets in placental vascular development unidentified
    • Whether this function is enzymatic untested here
  7. 2014 High

    Showed the essential epidermal barrier function is independent of prostasin's own enzymatic activity, redefining it as a non-catalytic role.

    Evidence Active-site serine-to-alanine knockin mice compared with null littermates

    PMID:24706745

    Open questions at the time
    • Did not identify the non-catalytic interactions mediating barrier function
    • Other prostasin functions could still be catalytic
  8. 2015 High

    Separated two prostasin functions: catalytic-independent barrier formation versus activation-cleavage-dependent hair follicle development.

    Evidence Zymogen-locked (cleavage-resistant) knockin mice compared with null and wild-type

    PMID:26719335

    Open questions at the time
    • Substrates underlying hair follicle defect unidentified
    • How a non-cleaved zymogen supports barrier function mechanistically unresolved
  9. 2020 High

    Established PRSS8 as a microbiota-dependent suppressor of TLR4/NF-κB inflammation in the intestinal epithelium.

    Evidence Intestinal epithelial-specific knockout in DSS colitis with TLR4/NF-κB readouts and antibiotic rescue

    PMID:31916038

    Open questions at the time
    • Direct molecular link between prostasin and TLR4 regulation unknown
    • Whether suppression is enzymatic untested
  10. 2021 High

    Quantified the relative contributions of scaffold versus proteolytic ENaC activation, showing the non-catalytic function suffices for baseline sodium homeostasis.

    Evidence Xenopus oocyte reconstitution with S238A and R44Q variants plus knockin mice challenged with triamterene

    PMID:33650216

    Open questions at the time
    • Identity of the scaffold-interacting partners on ENaC unknown
    • Context-dependence of proteolytic contribution incompletely mapped
  11. 2022 Medium

    Distinguished prostasin-dependent from prostasin-independent ENaC activation, showing nephrotic ENaC activation uses other filtered proteases.

    Evidence S238A and R44Q knockin mice in doxorubicin nephrotic syndrome with cleaved-ENaC and urinary prostasin readouts

    PMID:35312839

    Open questions at the time
    • Negative result; identity of the alternative proteases not established
    • Single-lab finding
  12. 2022 Medium

    Connected renal PRSS8 to endocrine control of aldosterone and the renin-angiotensin-aldosterone axis beyond direct channel regulation.

    Evidence Kidney tubule-specific knockout mice on varying Na+ diets with plasma aldosterone and renin measurements

    PMID:35743186

    Open questions at the time
    • Signal coupling ENaC activity to adrenal aldosterone unidentified
    • Single-lab finding
  13. 2023 Medium

    Reframed in vivo ENaC regulation by prostasin and matriptase as control of subunit protein abundance rather than direct proteolytic activation.

    Evidence St14 KO and double Prss8;St14 KO mice with ENaC/NCC Western blots and Na+/K+ balance

    PMID:37830556

    Open questions at the time
    • Mechanism controlling subunit abundance undefined
    • Single-lab finding
  14. 2025 Medium

    Showed renal prostasin participates in kidney-adrenal cross-talk regulating aldosterone synthase, overridable by potassium.

    Evidence Kidney tubule-specific knockout mice with dietary K+ supplementation and adrenal Cyp11b2 mRNA quantification

    PMID:40938892

    Open questions at the time
    • Nature of the inter-organ signal unidentified
    • Single-lab finding
  15. 2009 Medium

    Identified a non-enzymatic role for prostasin in promoting epithelial gene expression by upregulating E-cadherin and suppressing EMT.

    Evidence Re-expression of wild-type and protease-inactive prostasin in bladder TCC lines with E-cadherin and promoter methylation readouts

    PMID:19849847

    Open questions at the time
    • Mechanism linking prostasin to E-cadherin transcription unresolved
    • Single-lab cell-line study
  16. 2016 Medium

    Linked PRSS8 to suppression of Sphk1/S1P/Stat3/Akt signaling as a tumor suppressor in colorectal cancer.

    Evidence Overexpression/knockdown in CRC cells, Sphk1-/- mice, and xenografts

    PMID:27050145

    Open questions at the time
    • Direct molecular target in the Sphk1 pathway unidentified
    • Single-lab finding
  17. 2018 Medium

    Established PRSS8 as an intestinal suppressor of Wnt/β-catenin, EMT, and stem-cell oncogenic programs.

    Evidence Conditional intestinal knockout mice with spontaneous colitis/tumors, GSEA, and pathway Westerns

    PMID:30115975

    Open questions at the time
    • Whether tumor suppression is enzymatic untested here
    • Direct link to Wnt machinery undefined
  18. 2021 Low

    Proposed a SREBF2-PRSS8-SCNN1A axis driving ovarian cancer proliferation and EMT, contrasting with prostasin's tumor-suppressive roles elsewhere.

    Evidence Knockdown/overexpression in ovarian cancer lines with phenotypic assays and xenograft

    PMID:34823420

    Open questions at the time
    • No direct transcription-factor binding or promoter assay shown
    • Pathway inferred from expression changes only
  19. 2021 Low

    Linked PRSS8 to inhibition of JAK1/JAK2/STAT3 signaling in NSCLC tumor suppression.

    Evidence PRSS8 overexpression in A549 cells with phospho-JAK/STAT Westerns and xenografts

    PMID:27983914

    Open questions at the time
    • Placement based on protein-level changes without kinase assay or epistasis
    • Single-lab finding
  20. 2020 Low

    Placed PRSS8 downstream of epigenetic repression by a LINP1-EZH2/LSD1/DNMT1 complex in cervical cancer.

    Evidence RIP, knockdown/overexpression, rescue, and in vivo tumor assays

    PMID:32348690

    Open questions at the time
    • Abstract-level mechanistic detail
    • Direct promoter occupancy by the complex not demonstrated
  21. 2024 High

    Defined an OTUB1-YTHDF2-PRSS8-E-cadherin/β-catenin axis in which m6A-dependent mRNA degradation silences PRSS8.

    Evidence Ubiquitination assays, m6A-seq, mRNA stability, Co-IP, and cell/mouse functional studies in prostate cancer

    PMID:38462165

    Open questions at the time
    • Which m6A writer deposits the mark on PRSS8 not defined here
    • Mechanism by which PRSS8 controls E-cadherin non-enzymatically unresolved
  22. 2025 Medium

    Extended m6A-mediated PRSS8 destabilization to liver, linking loss of prostasin to TLR4-driven inflammation and stellate cell activation in fibrosis.

    Evidence MeRIP, m6A-site mutagenesis, and hepatocyte-HSC co-culture from a fibrosis model with inflammatory readouts

    PMID:40996077

    Open questions at the time
    • Direct mechanistic link between prostasin and TLR4 in hepatocytes unresolved
    • Single-lab finding
  23. 2026 Medium

    Identified PRSS8 as a TGFBR3 sheddase regulated by cholesterol homeostasis, connecting it to TGF-β signaling.

    Evidence TGFBR3 shedding assay with PRSS8 manipulation and cholesterol-pathway modulation

    PMID:42184470

    Open questions at the time
    • Direct demonstration of TGFBR3 cleavage site lacking at abstract level
    • How cholesterol regulates PRSS8 expression undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved which molecular substrates and binding partners mediate prostasin's catalytic-independent scaffold functions across barrier formation, ENaC regulation, and β-catenin/inflammatory signaling.
  • No identified non-catalytic interaction partner explaining barrier and ENaC scaffold roles
  • Mechanism coupling prostasin to E-cadherin transcription unknown
  • Signal mediating kidney-adrenal cross-talk unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 3 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-382551 Transport of small molecules 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2
Partners
F2RL1SPINT1SPINT2ST14TGFBR3YTHDF2

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Epidermal-specific knockout of CAP1/Prss8 in mice causes fatal postnatal dehydration with defects in stratum corneum lipid composition, corneocyte morphogenesis, profilaggrin processing, and loss of occludin from tight junctions, establishing that CAP1/Prss8 is required for epidermal permeability barrier formation. Conditional knockout mouse (skin-specific), skin permeability assays, transepidermal water loss measurements, immunohistochemistry for differentiation markers, lipid analysis, tight junction protein analysis The Journal of cell biology High 16061697
2007 Prostasin (PRSS8) is synthesized as an inactive zymogen that requires site-specific endoproteolytic cleavage for activation, and matriptase (a type II transmembrane serine protease) co-localizes with prostasin in nearly all normal epithelial tissues, consistent with matriptase acting as the upstream activator of prostasin in a cell-surface proteolytic cascade. Enzymatic gene trapping (beta-galactosidase knock-in at matriptase locus), immunohistochemistry, co-localization analysis across multiple epithelial tissue types Journal of cellular physiology Medium 17471493
2011 Transgenic overexpression of CAP1/Prss8 in mouse skin causes epidermal hyperplasia, ichthyosis, and inflammation; genetic ablation of PAR2 completely rescues all these phenotypes, establishing PAR2 as a downstream effector of CAP1/Prss8 in a signaling cascade governing skin homeostasis. Transgenic mouse (K14-CAP1/Prss8), PAR2-null genetic background cross, histology, TSLP measurement, immune cell infiltration analysis, epidermal barrier assays Nature communications High 21245842
2012 Genetic epistasis analysis shows that hypomorphic Prss8 mutations rescue embryonic lethality in HAI-1- and HAI-2-deficient mice, placing prostasin downstream of HAI-1/HAI-2-regulated matriptase. Paradoxically, biochemical analysis of placental tissues shows prostasin is required for matriptase zymogen activation, while prostasin zymogen activation is matriptase-independent in this context, revealing a mutual activation relationship. Genetic epistasis (combined Prss8 hypomorphic × HAI-1/HAI-2 KO mice), biochemical analysis (Western blot) of matriptase and prostasin activation state in placental tissues PLoS genetics High 22952456
2012 The V170D (mouse frizzy) and G54-P57 deletion (rat hairless) mutations in CAP1/Prss8 alter protein structure, modify glycosylation state, and reduce activation of ENaC, demonstrating that CAP1/Prss8 stimulates ENaC activity and that these natural mutations impair this function. In vitro ENaC activation assay, protein structure analysis, glycosylation assay, in vivo analysis of ENaC activity in distal colon (amiloride-sensitive current), histology The American journal of pathology High 22705055
2013 Constitutive knockout of CAP1/Prss8 leads to embryonic lethality with defective placental vascular development and incomplete cellular maturation of the labyrinth, while epiblast-specific deletion allows survival to birth, establishing a specific role for CAP1/Prss8 in placental labyrinth maturation. Constitutive and epiblast-specific conditional knockout mice, histology, immunohistochemistry, CAP1/Prss8 expression timing analysis (E13.5) PloS one High 23405214
2014 Mice homozygous for an active-site serine-to-alanine substitution rendering prostasin catalytically inactive (Prss8Cat-/Cat-) develop normal epidermal barrier function and survive to adulthood, demonstrating that prostasin executes its essential epidermal barrier function independent of its own enzymatic (serine protease) activity. Active-site mutagenesis (S→A knockin mice), comparison with prostasin-null mice in the same litters, barrier function assays, cutaneous wound healing The Journal of biological chemistry High 24706745
2015 Gene-edited mice expressing only zymogen-locked (activation-site cleavage-resistant) prostasin show normal interfollicular epidermal barrier development and postnatal survival, but defective whisker and pelage hair follicle formation, demonstrating that prostasin's epidermal barrier function does not require activation-site cleavage whereas hair follicle function requires proteolytic activation by matriptase. Gene editing to generate zymogen-locked knockin mice (activation site mutation), phenotypic analysis of epidermis and hair follicles, comparison with null and wild-type mice The Journal of biological chemistry High 26719335
2020 Intestinal epithelial cell-specific deletion of PRSS8 in mice exacerbates DSS-induced colitis and elevates TLR4 expression and NF-κB activation in colonic epithelial cells; broad-spectrum antibiotic treatment abolishes the exacerbation, establishing that prostasin suppresses TLR4-mediated NF-κB inflammatory signaling in a microbiota-dependent manner. Intestinal epithelial-specific Prss8 knockout mice (PRSS8ΔIEC), DSS colitis model, immunohistochemistry for TLR4, NF-κB activation assay, cytokine mRNA measurement, FITC-dextran permeability assay, antibiotic treatment Journal of gastroenterology High 31916038
2021 In Xenopus oocyte co-expression experiments, wild-type prostasin and the proteolytically inactive S238A mutant both cause maximal ENaC activation, whereas the zymogen-locked R44Q mutant causes only partial ENaC activation with reduced cell-surface proteolytic activity; in vivo, zymogen-locked Prss8-R44Q mice develop salt-wasting and renal failure upon ENaC inhibition, indicating prostasin contributes to proteolytic ENaC activation but its non-catalytic scaffold function is sufficient for baseline sodium homeostasis. Xenopus laevis oocyte co-expression system (ENaC + Prss8 variants), cell-surface proteolytic activity assay, knockin mice (S238A and R44Q), triamterene challenge, plasma electrolyte measurement Acta physiologica High 33650216
2022 In experimental nephrotic syndrome (doxorubicin model), ENaC proteolytic activation and sodium retention occur independently of prostasin activation and enzymatic activity, as shown by identical responses in Prss8-S238A and Prss8-R44Q knockin mice compared to wild-type, indicating other (aberrantly filtered) serine proteases mediate ENaC activation in nephrotic syndrome. Knockin mice (Prss8-S238A and Prss8-R44Q), doxorubicin nephrotic syndrome model, triamterene response, Western blot for cleaved ENaC subunits, urinary prostasin excretion Pflugers Archiv Medium 35312839
2022 Kidney tubule-specific CAP1/Prss8 knockout mice on Na+-deprived diet maintain ENaC-mediated sodium balance but show markedly reduced plasma aldosterone and shift to elevated plasma renin activity, demonstrating that renal CAP1/Prss8 is involved in coupling ENaC activation to aldosterone production and the renin-angiotensin-aldosterone axis. Kidney tubule-specific Prss8 knockout (Prss8PaxLC1), varying Na+ diets, plasma aldosterone and renin measurement, amiloride-sensitive rectal potential difference, ENaC subunit cleavage analysis International journal of molecular sciences Medium 35743186
2023 CAP3/St14 (matriptase) knockout mice exhibit significantly decreased CAP1/Prss8 protein expression and altered ENaC subunit abundances, and double CAP1/Prss8; CAP3/St14-deficient mice restore ENaC subunit protein abundance but reduce NCC activity, showing that these two serine proteases regulate ENaC predominantly at the level of protein abundance rather than direct proteolytic activation in vivo. CAP3/St14 KO mice, double CAP1/Prss8; CAP3/St14 KO mice, Western blot for ENaC subunits and NCC, RNAscope co-expression analysis, Na+/K+ balance measurements Cells Medium 37830556
2016 PRSS8 inhibits the Sphk1/S1P/Stat3/Akt signaling pathway in colorectal cancer cells; inverse association between PRSS8 and Sphk1 was demonstrated in human colorectal cancers and in Sphk1-/- mice, and PRSS8 overexpression suppressed tumor growth in nude mouse xenografts. PRSS8 overexpression and knockdown in colorectal cancer cells, Sphk1-/- mouse model, xenograft model, Western blot for pathway components Oncotarget Medium 27050145
2018 Conditional intestinal Prss8 knockout (Prss8fl/fl, p-Villin-Cre+) mice develop spontaneous colitis, intestinal tumors, and show increased Wnt/β-catenin signaling, EMT, and stem cell pathway activation, establishing PRSS8 as a suppressor of these oncogenic pathways in the intestinal epithelium. Conditional intestinal Prss8 KO mice, gene expression profiling, GSEA, Western blot for pathway markers, xenograft and in vitro functional assays, IHC on tissue microarrays Oncogene Medium 30115975
2009 Re-expression of prostasin (PRSS8) or a serine protease-inactive variant in bladder transitional cell carcinoma (TCC) cell lines that had lost prostasin expression resulted in transcriptional upregulation of E-cadherin, demonstrating a non-enzymatic role for prostasin in promoting epithelial gene expression and suppressing EMT. Prostasin re-expression (wild-type and protease-inactive mutant) in TCC cell lines, Western blot and qPCR for E-cadherin, methylation-specific PCR for promoter methylation BMC cancer Medium 19849847
2024 YTHDF2 binds PRSS8 mRNA and promotes its degradation in an m6A-dependent manner; the deubiquitinase OTUB1 stabilizes YTHDF2 protein by inhibiting its ubiquitination (independent of OTUB1 catalytic activity), thereby reducing PRSS8 expression. PRSS8 in turn decreases nuclear β-catenin through E-cadherin, independent of its protease activity, establishing an OTUB1–YTHDF2–PRSS8–E-cadherin/β-catenin axis in prostate cancer. In vivo and in vitro ubiquitination assays, m6A-sequencing, mRNA stability assays, Co-IP, cell and mouse model functional studies, Western blot for β-catenin and E-cadherin The Journal of biological chemistry High 38462165
2025 m6A modification of Prss8 mRNA decreases its stability, leading to reduced Prss8 protein in hepatocytes; mutation of the Prss8 m6A modification site restores Prss8 mRNA stability and protein levels, reduces TLR4, IL-1β, and IL-18 expression, and attenuates hepatic stellate cell activation, establishing that m6A-mediated mRNA destabilization of Prss8 promotes TLR4-driven inflammatory cascades in liver fibrosis. Methylated RNA immunoprecipitation (MeRIP), m6A site mutagenesis, primary hepatocyte–HSC co-culture from fibrosis mouse model, RT-qPCR, Western blot, ELISA for inflammatory markers DNA and cell biology Medium 40996077
2026 PRSS8 functions as an endogenous sheddase of the TGF-β co-receptor TGFBR3, and cholesterol homeostasis pathways regulate PRSS8 expression, thereby modulating TGF-β signaling through a cholesterol–PRSS8–TGFBR3 axis. TGFBR3 shedding assay, PRSS8 manipulation (overexpression/knockdown), cholesterol pathway modulation, functional TGF-β signaling assays Biochemical and biophysical research communications Medium 42184470
2021 SREBF2 transcriptionally activates PRSS8, and PRSS8 in turn promotes SCNN1A (ENaC α-subunit) expression, constituting a SREBF2–PRSS8–SCNN1A axis that promotes proliferation, migration, and EMT of ovarian cancer cells. PRSS8 and SREBF2 knockdown/overexpression in ovarian cancer cell lines, RT-qPCR, Western blot, MTT/colony formation/Transwell assays, in vivo xenograft Bioengineered Low 34823420
2021 PRSS8 inhibits JAK1/JAK2/STAT3 phosphorylation in NSCLC cells, and ectopic PRSS8 expression suppresses migration, invasion, EMT, and tumor growth in vitro and in vivo. PRSS8 overexpression in A549 NSCLC cells, Western blot for p-JAK1, p-JAK2, p-STAT3, xenograft model Oncology research Low 27983914
2025 In kidney tubule-specific CAP1/Prss8 knockout mice, supplementation with dietary K+ normalizes previously reduced plasma aldosterone and restores adrenal Cyp11b2 (aldosterone synthase) mRNA expression, indicating that renal prostasin participates in a kidney-adrenal cross-talk regulating aldosterone synthesis, and that this can be overridden by K+. Kidney tubule-specific Prss8 KO mice, dietary K+ supplementation, plasma aldosterone and renin measurement, adrenal Cyp11b2 mRNA quantification American journal of physiology. Renal physiology Medium 40938892
2024 Prss8 deficiency in mice causes impaired terminal erythroid differentiation, with reduced erythroblasts in placenta, yolk sac, and fetal liver, increased reticulocytes, and upregulation of ribosomal genes (Rpl/Rps) in erythroid progenitor cells within the AGM; prostasin's effect is cell-extrinsic as Prss8 is not expressed in erythroid cells but in ectoderm-like AGM cells, and yolk sac vascular remodeling is impaired. Prss8-/- embryo analysis at E11.5/E12.5, single-cell RNA sequencing of AGM, in vitro and in vivo erythroid differentiation assays, vascular remodeling analysis bioRxivpreprint Medium bio_10.1101_2024.10.25.620248
2020 LINP1 lncRNA recruits EZH2, LSD1, and DNMT1 to the PRSS8 promoter to repress its expression in cervical cancer; silencing LINP1 upregulates PRSS8, which inhibits cell proliferation and promotes apoptosis; inhibition of PRSS8 reverses these effects, placing PRSS8 downstream of epigenetic repression by the LINP1-EZH2/LSD1/DNMT1 complex. RIP assay, knockdown/overexpression in cervical cancer cell lines, qRT-PCR, loss-of-function rescue experiments, in vivo tumor growth assay Biochemistry and cell biology Low 32348690

Source papers

Stage 0 corpus · 34 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 The epidermal barrier function is dependent on the serine protease CAP1/Prss8. The Journal of cell biology 226 16061697
2011 PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin. Nature communications 95 21245842
2007 Co-localization of the channel activating protease prostasin/(CAP1/PRSS8) with its candidate activator, matriptase. Journal of cellular physiology 74 17471493
2012 Reduced prostasin (CAP1/PRSS8) activity eliminates HAI-1 and HAI-2 deficiency-associated developmental defects by preventing matriptase activation. PLoS genetics 62 22952456
1996 Structure and chromosomal localization of the human prostasin (PRSS8) gene. Genomics 49 8838796
2009 Loss of prostasin (PRSS8) in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT). BMC cancer 41 19849847
2016 Tumor suppressor PRSS8 targets Sphk1/S1P/Stat3/Akt signaling in colorectal cancer. Oncotarget 39 27050145
2012 Mutations of the serine protease CAP1/Prss8 lead to reduced embryonic viability, skin defects, and decreased ENaC activity. The American journal of pathology 34 22705055
2018 PRSS8 suppresses colorectal carcinogenesis and metastasis. Oncogene 32 30115975
2016 The serine protease prostasin (PRSS8) is a potential biomarker for early detection of ovarian cancer. Journal of ovarian research 32 27036110
2014 The membrane-anchored serine protease prostasin (CAP1/PRSS8) supports epidermal development and postnatal homeostasis independent of its enzymatic activity. The Journal of biological chemistry 29 24706745
2016 PRSS8 is Downregulated and Suppresses Tumour Growth and Metastases in Hepatocellular Carcinoma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 28 27915333
2010 The mouse frizzy (fr) and rat 'hairless' (frCR) mutations are natural variants of protease serine S1 family member 8 (Prss8). Experimental dermatology 27 20201958
2013 The channel-activating protease CAP1/Prss8 is required for placental labyrinth maturation. PloS one 26 23405214
2015 Distinct Developmental Functions of Prostasin (CAP1/PRSS8) Zymogen and Activated Prostasin. The Journal of biological chemistry 23 26719335
2016 PRSS8 methylation and its significance in esophageal squamous cell carcinoma. Oncotarget 21 27081034
2021 Zymogen-locked mutant prostasin (Prss8) leads to incomplete proteolytic activation of the epithelial sodium channel (ENaC) and severely compromises triamterene tolerance in mice. Acta physiologica (Oxford, England) 20 33650216
2020 LINP1 promotes the progression of cervical cancer by scaffolding EZH2, LSD1, and DNMT1 to inhibit the expression of KLF2 and PRSS8. Biochemistry and cell biology = Biochimie et biologie cellulaire 20 32348690
2021 Knocking down Sterol regulatory element binding protein 2 (SREBF2) inhibits the Serine Protease 8 (PRSS8) /sodium channel epithelial 1alpha subunit (SCNN1A) axis to reduce the cell proliferation, migration and epithelial-mesenchymal transformation of ovarian cancer. Bioengineered 16 34823420
2022 Sodium retention in nephrotic syndrome is independent of the activation of the membrane-anchored serine protease prostasin (CAP1/PRSS8) and its enzymatic activity. Pflugers Archiv : European journal of physiology 14 35312839
2016 Protease Serine S1 Family Member 8 (PRSS8) Inhibits Tumor Growth In Vitro and In Vivo in Human Non-Small Cell Lung Cancer. Oncology research 13 27983914
2022 Overexpressed lncRNA LINC00893 Suppresses Progression of Colon Cancer by Binding with miR-146b-3p to Upregulate PRSS8. Journal of oncology 12 35571488
2020 Sodium absorption stimulator prostasin (PRSS8) has an anti-inflammatory effect via downregulation of TLR4 signaling in inflammatory bowel disease. Journal of gastroenterology 12 31916038
2016 Altered Prostasin (CAP1/Prss8) Expression Favors Inflammation and Tissue Remodeling in DSS-induced Colitis. Inflammatory bowel diseases 11 27755216
2022 Kidney-Specific CAP1/Prss8-Deficient Mice Maintain ENaC-Mediated Sodium Balance through an Aldosterone Independent Pathway. International journal of molecular sciences 10 35743186
2024 YTHDF2 protein stabilization by the deubiquitinase OTUB1 promotes prostate cancer cell proliferation via PRSS8 mRNA degradation. The Journal of biological chemistry 9 38462165
2023 PRSS8, encoding prostasin, is mutated in patients with autosomal recessive ichthyosis. Human genetics 8 36715754
2024 Potential Plasma Proteins (LGALS9, LAMP3, PRSS8 and AGRN) as Predictors of Hospitalisation Risk in COVID-19 Patients. Biomolecules 4 39334929
2023 Kidney-Specific Membrane-Bound Serine Proteases CAP1/Prss8 and CAP3/St14 Affect ENaC Subunit Abundances but Not Its Activity. Cells 4 37830556
2024 Circ_0001741 exerts as a tumor promoter in ovarian cancer through the regulation of miR-491-5p/PRSS8 axis. Discover oncology 1 39527152
2015 [Prostasin (PRSS8) as a new pathological factor]. Nihon rinsho. Japanese journal of clinical medicine 1 25812384
2026 Human PRSS8 functions as a targetable, endogenous TGFBR3 sheddase via the novel cholesterol-PRSS8-TGF-β axis. Biochemical and biophysical research communications 0 42184470
2025 Dietary K+ supplementation restores normal aldosterone level in Na+-deprived renal tubule-specific CAP1/Prss8-deficient mice. American journal of physiology. Renal physiology 0 40938892
2025 m6A Modification Destabilizes Prss8 and Activates Hepatic Stellate Cells via TLR4-Mediated Inflammatory Responses. DNA and cell biology 0 40996077

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