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Gene Section
Review
PRSS8 (protease, serine, 8)
Li-Mei Chen, Karl X Chai
Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, FL
32816, USA (LMC, KXC)
Published in Atlas Database: April 2012
Online updated version : http://AtlasGeneticsOncology.org/Genes/PRSS8ID41880ch16p11.html
DOI: 10.4267/2042/47537
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Transcription
Identity
Description: The full-length human prostasin mRNA,
as deduced from a cloned cDNA, contains a 1032nucleotide (nt) open-reading frame that can be
translated into 343 AA, a 138-nt 5'-UTR, and a 572-nt
3'-UTR (Yu et al., 1995).
Expression: In humans, prostasin mRNA expression
was detected by reverse-transcription coupled
polymerase chain reaction (RT-PCR) in the total RNA
of the prostate, liver, salivary gland, kidney, lung,
pancreas, colon, bronchus, and renal proximal tubular
cells (Yu et al., 1995). In the human prostate, the
prostasin mRNA was localized to the epithelial cells.
The urinary bladder epithelial (urothelial) cells of the
human and the mouse express the prostasin mRNA and
the translated protein (Chen et al., 2009b; Chen et al.,
2006a). Human breast epithelial cells also express the
prostasin mRNA and the translated protein (Chen and
Chai, 2002; Bergum et al., 2012). Prostasin mRNA is
expressed in the rhesus monkey endometrial glandular
epithelium on Day 12 and Day 18 of pregnancy, and in
the placental villi, trophoblastic column, trophoblastic
shell, and the fetal-maternal border on Day 18 and Day
26 (Lin et al., 2006). The endometrial prostasin
expression subsides but the placental expression
increases further along the gestational course.
Expression regulation: In the mouse renal cortical
collecting duct M-1 cells prostasin mRNA expression
can be up-regulated by aldosterone treatment, which is
also a mechanism of increasing urinary prostasin
excretion in rats following whole-animal infusion
(Narikiyo et al., 2002). Aldosterone infusion was
shown to induce prostasin mRNA expression in the left
colon of the rat as well (Fukushima et al., 2004).
Prostasin mRNA (and protein) expression in the M-1
cells can be repressed by transforming growth factor
Other names: CAP1, PROSTASIN
HGNC (Hugo): PRSS8
Location: 16p11.2
Local order: Centromere to telomere.
DNA/RNA
Description
The human prostasin/PRSS8 gene consists of six (6)
exons and five (5) introns. A 7-Kb (kilobase) genomic
region containing the human prostasin/PRSS8 gene was
fully sequenced in the original cloning report (Yu et al.,
1996), with a 1.4-kb 5'-flanking region and a 1.2-kb 3'flanking region. A single chromosomal location at
16p11.2 was reported to harbor the human
prostasin/PRSS8 gene.
The mouse orthologue of the prostasin/prss8 gene,
located on Chromosome 7, is highly homologous to the
human prostasin/PRSS8 gene, with a six-exon
organization (Verghese et al., 2004). The mouse
prostasin/prss8 gene's 3'-untranslated region (UTR)
overlaps with the 3'-UTR of the Myst1 histone
acetyltransferase gene. Genetic mapping evidence
provided support for the rat 'fuzzy' and 'hairless'
mutations to be orthologues of the mouse 'frizzy'
mutation (Ahearn et al., 2002). A T/A transversion
missense mutation, changing a Val to an Asp at amino
acid (AA) residue 170 of the mouse prostasin, was
shown to be causative to the mutant 'frizzy' phenotype
(Spacek et al., 2010). The 'hairless' rat has a 12-bp
(base pair) deletion in the third exon of the prss8 gene's
coding region, whereas the 'fuzzy' rat does not have any
prss8 coding sequence changes.
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beta-1 (TGF-b1), via down-regulating the NF-kB
signalling (Tuyen et al., 2005). In the mouse urinary
bladder, prostasin mRNA expression is down-regulated
in association with inflammation caused by
intraperitoneal
injection
of
bacterial
lipopolysaccharides (LPS) (Chen et al., 2006a).
Promoter DNA hypermethylation and histone
deacetylation are epigenetic mechanisms that downregulate prostasin mRNA transcription in human breast
and prostate cancer cell lines (Chen and Chai, 2002;
Chen et al., 2004). Nerve growth factor (NGF) induces
prostasin mRNA expression in human prostate cancer
cell lines (DU-145 and PC-3) with epigenetically
repressed prostasin expression (Chen et al., 2004). The
sterol regulatory element-binding proteins (SREBPs)
SREBP-1c and SREBP-2 are positive transcriptional
regulators of prostasin expression in human epithelial
cell lines (Chen et al., 2006b), and the binding sites of
SREBP-2 in the human prostasin/PRSS8 gene promoter
region have been determined (Chen et al., 2006c). The
SNAIL family zinc-finger transcription factors SNAIL
and SLUG are negative regulators of prostasin
transcription in human epithelial cell lines (Chen et al.,
2006b). The SREBPs and SLUG are responsive to
dihydrotestosterone (DHT) with up-regulation of
expression and thus making the prostasin/PRSS8 gene
indirectly responsive to androgen regulation (Chen et
al., 2006b).
Localisation
A glycosylphosphatidylinositol (GPI) anchor tethers
the mature prostasin protein to the plasma membrane
(Chen et al., 2001b). The mature prostasin protein can
be
released
from
the
membrane
by
phosphatidylinositol-specific phospholipase C (Chen et
al., 2001b), or GPI-specific phospholipase D1 (Gpld1)
(Verghese et al., 2006). But in the kidney shedding of
prostasin from the cell membrane may be peptidasedependent (Verghese et al., 2006). In the epithelium
proteolytic cleavage of the pro-prostasin by matriptase
must occur at the basolateral membrane but
transcytosis brings the GPI-anchored prostasin to its
major cellular location, the apical membrane (Friis et
al., 2011).
Function
Prostasin was first identified as a serine protease in
human seminal fluid, purified by the use of aprotininaffinity chromatography (Yu et al., 1994). This native
purified form of human prostasin displayed a trypsinlike proteolytic activity with a pH optimum of 9.0 on
some synthetic substrates. The serine protease catalytic
triad of the human prostasin was deduced after the
cloning of its cDNA, as His53/Asp102/Ser206 (Yu et
al., 1995). A Ser206Ala mutant of the human prostasin
was used to confirm the serine active site (Chen et al.,
2008). Using a recombinant human prostasin catalytic
domain (i.e., lacking the GPI anchor and cellular
context) produced in insect cells, the substrate
specificity at the P1 position was determined to be
either Arg or Lys (Shipway et al., 2004). The S1
substrate subsite loop of human prostasin was found to
bind divalent ions such as Ca++ in a crystallized form
with protease inhibitors, suggesting that divalent
cations can regulate the protease activity (Spraggon et
al., 2009).
Natural substrates: ENaC - The first candidate
physiological substrate of prostasin was identified in a
Xenopus kidney epithelial cell line (A6) in a functional
cloning assay to find proteolytic activators of the
epithelial sodium channel (ENaC), thus earning the
nickname CAP1 (channel-activating protease 1) for
prostasin (Vallet et al., 1997). The rat prostasin, when
co-expressed with rat ENaC in Xenopus oocytes
produces increased amiloride-sensitive sodium current,
indicating ENaC activation by the co-expressed
prostasin (Adachi et al., 2001). Activation of ENaC in
the Xenopus oocyte requires the GPI-anchorage of the
xCAP1 (Xenopus CAP1), indicating an extracellular
location for the proteolytic activation of ENaC by
xCAP1/prostasin (Vallet et al., 2002). Using a nasal
epithelial cell line JMF/CF15 homozygous for the
∆F508 cystic fibrosis mutation, prostasin downregulation by small-interfering RNA (siRNA) was
shown to drop ENaC currents by >70% (Tong et al.,
2004).
Pseudogene
No prostasin/PRSS8 pseudogene has been identified to
date.
Protein
Description
The mature form of the human prostasin is 40 kDa in
size as determined by SDS-PAGE, and has a pI in the
range of 4.5-4.8 (Yu et al., 1994). The pro-peptide of
the human prostasin is 311 AA in length (Yu et al.,
1995), and it is cleaved at Arg12 in the sequence of
Gln-Ala-Arg-Ile by matriptase, hepsin, or plasmin
(Chen et al., 2010a; Svenningsen et al., 2009) to
produce a two-chain (12 AA and 277 AA) disulphidelinked mature protein (Yu et al., 1995).
Expression
In humans the prostasin protein could be detected by
radioimmunoassay (RIA) in tissue extracts of the
prostate, colon, lung, kidney, pancreas, salivary gland,
liver, and bronchi, as well as in seminal fluid and urine;
but not in tissue extracts of the brain, muscle, testis,
ventricle, atrium, or aorta (Yu et al., 1994). By
immunohistochemistry (IHC), human prostasin has
been detected in the epithelial cells of the prostate (Yu
et al., 1994; Chen et al., 2001a), the urinary bladder
(Chen et al., 2009b), and the breast (Bergum et al.,
2012); and the placenta trophoblasts during early
pregnancy (Ma et al., 2009).
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PRSS8 (protease, serine, 8)
Chen LM, Chai KX
with testisin (Hooper et al., 1999) and gamma tryptase
(Caughey et al., 2000).
The human prostasin cleaves the gamma subunit of
ENaC at RKRK(186) (Carattino et al., 2008). In the
mouse however, ENaC activation by mCAP1 (mouse
CAP1) does not require its catalytic/proteolytic
function, though the GPI anchorage is still required for
mCAP1 in this role (Andreasen et al., 2006).
Natural substrates: Matriptase - While an activating
protease for pro-prostasin, matriptase has also been
shown to be a substrate of prostasin in mouse lung
fibroblast cells and human keratinocytes with the use of
soluble recombinant active human prostasin (Camerer
et al., 2010).
This mechanism explains the activation of proteaseactivated receptor 2 (PAR-2) upon addition of the
soluble active prostasin, which accomplishes the PAR2 activation via activating matriptase, a direct PAR-2
activating protease. This mechanism also helps explain
the enhancement of matriptase cleavage of the
extracellular domain (ECD) of the epidermal growth
factor receptor (EGFR), which was first thought to be
potentially cleaved by prostasin as well (Chen et al.,
2008), but later proven not to be the case (Chen et al.,
2010a).
In human prostate epithelial cells however, prostasin
also negatively regulate PAR-2 signalling, an action
that requires prostasin's serine active site but not its
GPI anchor (Chen et al., 2009a).
Inhibitors: As a serine protease, the purified form of
the human prostasin can be inhibited by aprotinin,
antipain, leupeptin, and benzamidine (Yu et al., 1994).
In the serpin-class serine protease inhibitors, protease
nexin 1 (PN-1) is the cognate serpin for prostasin,
forming a covalent complex with the latter to achieve
inhibition of its serine protease activity (Chen et al.,
2004).
In the human PN-1 reactive site, the Leu-Ile-Ala-Arg
residues at the P4-P1 positions of this suicide inhibitor
should represent also the optimal substrate for
prostasin. A Kunitz-type reversible serine protease
inhibitor, hepatocyte growth factor activator inhibitor 1
(HAI-1) is a physiologically relevant inhibitor of
prostasin (Fan et al., 2005; Chen et al., 2010b), whereas
HAI-2 can inhibit the prostasin protease domain in
vitro (Shipway et al., 2004).
The synthetic serine protease inhibitor camostat
mesilate and its active metabolite FOY-251 can inhibit
prostasin serine protease activity in vitro (Maekawa et
al., 2009), and possibly in vivo as well (Coote et al.,
2009).
Mutations
Germinal
In mice, homozygous loss of the prostasin/prss8 gene is
embryonically lethal so conditional knockouts are
needed for investigating prostasin/prss8 functions in
vivo (Rubera et al., 2002).
In humans, no Mendelian hereditary conditions on the
basis of prostasin/PRSS8 gene mutations have been
described to date.
A transcribed single nucleotide polymorphism (tSNP)
in the human prostasin/PRSS8 gene (rs12597511: C;T)
shows genotype association with hypertension (Zhu et
al., 2008).
A missense SNP, E342K, of the human
prostasin/PRSS8 gene has been reported (Li et al.,
2011). Another human prostasin/PRSS8 gene SNP,
2827 G>A, was reported to show genotype association
with body mass index (BMI), OGTT-2h glucose, IRT3h insulin, and serum potassium (Li et al., 2011).
Implicated in
Prostate cancer
Note
Prostasin expression is down-regulated in high-grade
prostate cancers, and correspondingly in highly
invasive human and mouse prostate cancer cell lines
(Chen et al., 2001a).
Re-expression of prostasin in highly invasive human
prostate cancer cell lines (DU-145 and PC-3) reduced
their in vitro invasion.
Down-regulated prostasin expression was associated
with metastatic and hormone-refractory prostate
cancers in a small study involving 54 cases (Takahashi
et al., 2003).
This study confirmed the inverse correlation of
prostasin expression with histological differentiation
but failed to find correlations with clinical staging.
Another small study (96 cases and 86 controls)
suggested that RT-PCR amplification of the prostasin
mRNA from circulating tumor cells may be applicable
as a method for early diagnosis of prostate cancer cell
dissemination (Laribi et al., 2001).
Breast cancer
Note
A coordinated co-expression pattern in human breast
cancers has been reported for prostasin and its
activating enzyme/substrate matriptase (Bergum et al.,
2012). Prostasin expression is down-regulated in highly
invasive human breast cancer cells whereas reexpression of prostasin in these cells reduced their in
vitro invasion (Chen and Chai, 2002).
Homology
The human prostasin was shown to share sequence
homology at the amino acid level with acrosin, plasma
kallikrein, and hepsin upon sequencing of its full-length
cDNA (Yu et al., 1995).
Prostasin also shares amino acid sequence homology
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prostasin in primary aldosteronism patients is
significantly increased (Narikiyo et al., 2002). Rats
receiving tail-vein injection of adenoviruses carrying a
human prostasin transgene expressed the transgene
ubiquitously and showed elevated plasma aldosterone
and hypertension along with reduced urinary potassium
excretion and increased urinary sodium and kallikrein
excretion (Wang et al., 2003). Prostasin regulates
aldosterone production in human adrenocortical H295R
cells by a protease-independent but calcium- and
protein kinase C (PKC) dependent mechanism (Ko et
al., 2010).
Ovarian cancer
Note
Prostasin is detected by IHC more intensely in the
epithelial and stromal cells of cancerous ovarian tissues
than those of normal ovarian tissues (Mok et al., 2001).
Serum prostasin levels may be applicable as a highly
sensitive and specific marker for detecting ovarian
cancer. Another study also revealed serum prostasin as
a potentially informative marker for ovarian cancer
(Yip et al., 2011).
Colon cancer
Urinary prostasin
Note
Prostasin mRNA expression was found to be correlated
to prolonged survival after surgery in colon cancer
patients in a small study (Cavalieri et al., 2007). In
tissues from the same colon cancer patients, prostasin
mRNA expression was found to be slightly increased in
the cancerous sections whereas membrane localization
of the prostasin protein in colon cancer tissues appears
to be disturbed as well (Selzer-Plon et al., 2009).
Note
Urinary prostasin level may be applicable as a marker
for upstream ENaC activation and this marker is
increased in primary aldosteronism patients after
volume expansion (Olivieri et al., 2005). Another study
also indicated a strong correlation between urinary
prostasin levels and urinary or plasma aldosterone
levels in hypertensive patients (Koda et al., 2009).
Other cancers
Cystic fibrosis (CF)
Note
Prostasin is among five (5) genes that can be used for
separating the chromophobe renal cell carcinoma
(RCC) from oncocytoma based on their differential
mRNA expression in these two tumor types (Rohan et
al., 2006). In the human hepatoma cell line HepG2
prostasin mRNA expression can be reduced by poly
unsaturated fatty acids (Fujiwara et al., 2003).
Note
ENaC function related condition.
Disease
Prostasin was found to be a major regulator of ENaCmediated sodium current in a human epithelial cell line
carrying the ∆F508 CF mutation (Tong et al., 2004). In
this context, prostasin expression in human airway
epithelial cells can be regulated by the airway surface
liquid (ASL) volume and CF patients express >50%
more prostasin in their airway epithelial cells than nonCF subjects (Myerburg et al., 2008).
Inflammation
Disease
Prostasin expression in the urinary bladder is downregulated by LPS-induced inflammation marked by the
characteristic up-regulation of the inducible nitric oxide
synthase (iNOS) expression (Chen et al., 2006a).
Forced expression of prostasin in the bladder urothelial
cells attenuated the iNOS induction. Silencing prostasin
expression in the human benign prostatic hyperplasia
cell line BPH-1 is associated with up-regulation of
iNOS expression as well as that of interleukins 6 and 8
(IL-6 and IL-8) (Chen et al., 2009a). In the mouse
kidney cortical collecting duct M-1 cells, treatment
with IL-6 was shown to increase prostasin protein
expression (Li et al., 2010). Transgenic mice overexpressing prostasin in the skin show skin
inflammation and ichthyosis, phenotypes that are not
manifested in PAR-2 null mice, indicating a PAR-2
mediated mechanism for prostasin's role in skin
inflammation (Frateschi et al., 2011).
Epidermal/Epithelial terminal
differentiation
Disease
Mice born with a prostasin/prss8 knockout in the skin
die within 60 hours, presenting a phenotype of severely
malformed stratum corneum (SC) (Leyvraz et al.,
2005). This defect results in impaired skin barrier
function manifested as increased skin permeability and
dehydration. At the molecular level, occludin is absent
among the tight junction (TJ) proteins thus preventing
the proper formation of the tight junctions and terminal
differentiation of the epidermis. Along the same line of
reasoning, the renal collecting duct epithelium requires
apically expressed, GPI-anchored, and lipid-raftassociated active prostasin serine protease for
establishment of high transepithelial resistance (TER),
an indicator of epithelial terminal differentiation
(Steensgaard et al., 2010).
Aldosteronism and hypertension
Note
ENaC function related condition.
Disease
Consistent with aldosterone's transcriptional activator
role on prostasin expression, urinary excretion of
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(9)
References
Yu JX, Chao L, Chao J. Prostasin is a novel human serine
proteinase from seminal fluid. Purification, tissue distribution,
661
PRSS8 (protease, serine, 8)
Chen LM, Chai KX
and localization in prostate gland. J Biol Chem. 1994 Jul
22;269(29):18843-8
required for activation of ENaC in the Xenopus oocyte. J Am
Soc Nephrol. 2002 Mar;13(3):588-94
Yu JX, Chao L, Chao J. Molecular cloning, tissue-specific
expression, and cellular localization of human prostasin
mRNA. J Biol Chem. 1995 Jun 2;270(22):13483-9
Fujiwara Y, Yokoyama M, Sawada R, Seyama Y, Ishii M,
Tsutsumi S, Aburatani H, Hanaka S, Itakura H, Matsumoto A.
Analysis of the comprehensive effects of polyunsaturated fatty
acid on mRNA expression using a gene chip. J Nutr Sci
Vitaminol (Tokyo). 2003 Apr;49(2):125-32
Yu JX, Chao L, Ward DC, Chao J. Structure and chromosomal
localization of the human prostasin (PRSS8) gene. Genomics.
1996 Mar 15;32(3):334-40
Takahashi S, Suzuki S, Inaguma S, Ikeda Y, Cho YM, Hayashi
N, Inoue T, Sugimura Y, Nishiyama N, Fujita T, Chao J,
Ushijima T, Shirai T. Down-regulated expression of prostasin in
high-grade or hormone-refractory human prostate cancers.
Prostate. 2003 Feb 15;54(3):187-93
Vallet V, Chraibi A, Gaeggeler HP, Horisberger JD, Rossier
BC. An epithelial serine protease activates the amiloridesensitive sodium channel. Nature. 1997 Oct 9;389(6651):60710
Wang C, Chao J, Chao L. Adenovirus-mediated human
prostasin gene delivery is linked to increased aldosterone
production and hypertension in rats. Am J Physiol Regul Integr
Comp Physiol. 2003 Apr;284(4):R1031-6
Hooper JD, Nicol DL, Dickinson JL, Eyre HJ, Scarman AL,
Normyle JF, Stuttgen MA, Douglas ML, Loveland KA,
Sutherland GR, Antalis TM. Testisin, a new human serine
proteinase expressed by premeiotic testicular germ cells and
lost in testicular germ cell tumors. Cancer Res. 1999 Jul
1;59(13):3199-205
Chen LM, Zhang X, Chai KX. Regulation of prostasin
expression and function in the prostate. Prostate. 2004 Apr
1;59(1):1-12
Caughey GH, Raymond WW, Blount JL, Hau LW, Pallaoro M,
Wolters PJ, Verghese GM. Characterization of human gammatryptases, novel members of the chromosome 16p mast cell
tryptase and prostasin gene families. J Immunol. 2000 Jun
15;164(12):6566-75
Fukushima K, Naito H, Funayama Y, Yonezawa H, Haneda S,
Shibata C, Sasaki I. In vivo induction of prostasin mRNA in
colonic epithelial cells by dietary sodium depletion and
aldosterone infusion in rats. J Gastroenterol. 2004
Oct;39(10):940-7
Adachi M, Kitamura K, Miyoshi T, Narikiyo T, Iwashita K,
Shiraishi N, Nonoguchi H, Tomita K. Activation of epithelial
sodium channels by prostasin in Xenopus oocytes. J Am Soc
Nephrol. 2001 Jun;12(6):1114-21
Shipway A, Danahay H, Williams JA, Tully DC, Backes BJ,
Harris JL. Biochemical characterization of prostasin, a channel
activating protease. Biochem Biophys Res Commun. 2004 Nov
12;324(2):953-63
Chen LM, Hodge GB, Guarda LA, Welch JL, Greenberg NM,
Chai KX. Down-regulation of prostasin serine protease: a
potential invasion suppressor in prostate cancer. Prostate.
2001a Jul 1;48(2):93-103
Tong Z, Illek B, Bhagwandin VJ, Verghese GM, Caughey GH.
Prostasin, a membrane-anchored serine peptidase, regulates
sodium currents in JME/CF15 cells, a cystic fibrosis airway
epithelial cell line. Am J Physiol Lung Cell Mol Physiol. 2004
Nov;287(5):L928-35
Chen LM, Skinner ML, Kauffman SW, Chao J, Chao L, Thaler
CD, Chai KX. Prostasin is a glycosylphosphatidylinositolanchored active serine protease. J Biol Chem. 2001b Jun
15;276(24):21434-42
Verghese GM, Tong ZY, Bhagwandin V, Caughey GH. Mouse
prostasin gene structure, promoter analysis, and restricted
expression in lung and kidney. Am J Respir Cell Mol Biol. 2004
Apr;30(4):519-29
Laribi A, Berteau P, Gala J, Eschwège P, Benoit G, Tombal B,
Schmitt F, Loric S. Blood-borne RT-PCR assay for prostasinspecific transcripts to identify circulating prostate cells in
cancer patients. Eur Urol. 2001 Jan;39(1):65-71
Fan B, Wu TD, Li W, Kirchhofer D. Identification of hepatocyte
growth factor activator inhibitor-1B as a potential physiological
inhibitor of prostasin. J Biol Chem. 2005 Oct
14;280(41):34513-20
Mok SC, Chao J, Skates S, Wong K, Yiu GK, Muto MG,
Berkowitz RS, Cramer DW. Prostasin, a potential serum
marker for ovarian cancer: identification through microarray
technology. J Natl Cancer Inst. 2001 Oct 3;93(19):1458-64
Leyvraz C, Charles RP, Rubera I, Guitard M, Rotman S,
Breiden B, Sandhoff K, Hummler E. The epidermal barrier
function is dependent on the serine protease CAP1/Prss8. J
Cell Biol. 2005 Aug 1;170(3):487-96
Ahearn K, Akkouris G, Berry PR, Chrissluis RR, Crooks IM,
Dull AK, Grable S, Jeruzal J, Lanza J, Lavoie C, Maloney RA,
Pitruzzello M, Sharma R, Stoklasek TA, Tweeddale J, King TR.
The Charles River "hairless" rat mutation maps to chromosome
1: allelic with fuzzy and a likely orthologue of mouse frizzy. J
Hered. 2002 May-Jun;93(3):210-3
Olivieri O, Castagna A, Guarini P, Chiecchi L, Sabaini G,
Pizzolo F, Corrocher R, Righetti PG. Urinary prostasin: a
candidate marker of epithelial sodium channel activation in
humans. Hypertension. 2005 Oct;46(4):683-8
Chen LM, Chai KX. Prostasin serine protease inhibits breast
cancer invasiveness and is transcriptionally regulated by
promoter DNA methylation. Int J Cancer. 2002 Jan
20;97(3):323-9
Tuyen DG, Kitamura K, Adachi M, Miyoshi T, Wakida N,
Nagano J, Nonoguchi H, Tomita K. Inhibition of prostasin
expression by TGF-beta1 in renal epithelial cells. Kidney Int.
2005 Jan;67(1):193-200
Narikiyo T, Kitamura K, Adachi M, Miyoshi T, Iwashita K,
Shiraishi N, Nonoguchi H, Chen LM, Chai KX, Chao J, Tomita
K. Regulation of prostasin by aldosterone in the kidney. J Clin
Invest. 2002 Feb;109(3):401-8
Andreasen D, Vuagniaux G, Fowler-Jaeger N, Hummler E,
Rossier BC. Activation of epithelial sodium channels by mouse
channel activating proteases (mCAP) expressed in Xenopus
oocytes requires catalytic activity of mCAP3 and mCAP2 but
not mCAP1. J Am Soc Nephrol. 2006 Apr;17(4):968-76
Rubera I, Meier E, Vuagniaux G, Mérillat AM, Beermann F,
Rossier BC, Hummler E. A conditional allele at the mouse
channel activating protease 1 (Prss8) gene locus. Genesis.
2002 Feb;32(2):173-6
Chen LM, Wang C, Chen M, Marcello MR, Chao J, Chao L,
Chai KX. Prostasin attenuates inducible nitric oxide synthase
expression in lipopolysaccharide-induced urinary bladder
inflammation. Am J Physiol Renal Physiol. 2006a
Sep;291(3):F567-77
Vallet V, Pfister C, Loffing J, Rossier BC. Cell-surface
expression of the channel activating protease xCAP-1 is
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(9)
662
PRSS8 (protease, serine, 8)
Chen LM, Chai KX
Chen M, Chen LM, Chai KX. Androgen regulation of prostasin
gene expression is mediated by sterol-regulatory elementbinding proteins and SLUG. Prostate. 2006b Jun 15;66(9):91120
Ma XJ, Fu YY, Li YX, Chen LM, Chai K, Wang YL. Prostasin
inhibits cell invasion in human choriocarcinomal JEG-3 cells.
Histochem Cell Biol. 2009 Dec;132(6):639-46
Maekawa A, Kakizoe Y, Miyoshi T, Wakida N, Ko T, Shiraishi
N, Adachi M, Tomita K, Kitamura K. Camostat mesilate inhibits
prostasin activity and reduces blood pressure and renal injury
in
salt-sensitive
hypertension.
J
Hypertens.
2009
Jan;27(1):181-9
Chen M, Chen LM, Chai KX. Mechanisms of sterol regulatory
element-binding protein-2 (SREBP-2) regulation of human
prostasin gene expression. Biochem Biophys Res Commun.
2006c Aug 11;346(4):1245-53
Lin HY, Zhang H, Yang Q, Wang HX, Wang HM, Chai KX,
Chen LM, Zhu C. Expression of prostasin and protease nexin-1
in rhesus monkey (Macaca mulatta) endometrium and placenta
during early pregnancy. J Histochem Cytochem. 2006
Oct;54(10):1139-47
Selzer-Plon J, Bornholdt J, Friis S, Bisgaard HC, Lothe IM,
Tveit KM, Kure EH, Vogel U, Vogel LK. Expression of prostasin
and its inhibitors during colorectal cancer carcinogenesis. BMC
Cancer. 2009 Jun 25;9:201
Spraggon G, Hornsby M, Shipway A, Tully DC, Bursulaya B,
Danahay H, Harris JL, Lesley SA. Active site conformational
changes of prostasin provide a new mechanism of protease
regulation by divalent cations. Protein Sci. 2009
May;18(5):1081-94
Rohan S, Tu JJ, Kao J, Mukherjee P, Campagne F, Zhou XK,
Hyjek E, Alonso MA, Chen YT. Gene expression profiling
separates chromophobe renal cell carcinoma from oncocytoma
and identifies vesicular transport and cell junction proteins as
differentially expressed genes. Clin Cancer Res. 2006 Dec
1;12(23):6937-45
Svenningsen P, Uhrenholt TR, Palarasah Y, Skjødt K, Jensen
BL, Skøtt O. Prostasin-dependent activation of epithelial Na+
channels by low plasmin concentrations. Am J Physiol Regul
Integr Comp Physiol. 2009 Dec;297(6):R1733-41
Verghese GM, Gutknecht MF, Caughey GH. Prostasin
regulates epithelial monolayer function: cell-specific Gpld1mediated secretion and functional role for GPI anchor. Am J
Physiol Cell Physiol. 2006 Dec;291(6):C1258-70
Chen M, Chen LM, Lin CY, Chai KX. Hepsin activates
prostasin and cleaves the extracellular domain of the
epidermal growth factor receptor. Mol Cell Biochem. 2010a
Apr;337(1-2):259-66
Cavalieri D, Dolara P, Mini E, Luceri C, Castagnini C, Toti S,
Maciag K, De Filippo C, Nobili S, Morganti M, Napoli C, Tonini
G, Baccini M, Biggeri A, Tonelli F, Valanzano R, Orlando C,
Gelmini S, Cianchi F, Messerini L, Luzzatto L. Analysis of gene
expression profiles reveals novel correlations with the clinical
course of colorectal cancer. Oncol Res. 2007;16(11):535-48
Chen YW, Wang JK, Chou FP, Chen CY, Rorke EA, Chen LM,
Chai KX, Eckert RL, Johnson MD, Lin CY. Regulation of the
matriptase-prostasin cell surface proteolytic cascade by
hepatocyte growth factor activator inhibitor-1 during epidermal
differentiation. J Biol Chem. 2010b Oct 8;285(41):31755-62
Carattino MD, Hughey RP, Kleyman TR. Proteolytic processing
of the epithelial sodium channel gamma subunit has a
dominant role in channel activation. J Biol Chem. 2008 Sep
12;283(37):25290-5
Camerer E, Barker A, Duong DN, Ganesan R, Kataoka H,
Cornelissen I, Darragh MR, Hussain A, Zheng YW, Srinivasan
Y, Brown C, Xu SM, Regard JB, Lin CY, Craik CS, Kirchhofer
D, Coughlin SR. Local protease signaling contributes to neural
tube closure in the mouse embryo. Dev Cell. 2010 Jan
19;18(1):25-38
Chen M, Chen LM, Lin CY, Chai KX. The epidermal growth
factor receptor (EGFR) is proteolytically modified by the
Matriptase-Prostasin serine protease cascade in cultured
epithelial cells. Biochim Biophys Acta. 2008 May;1783(5):896903
Ko T, Kakizoe Y, Wakida N, Hayata M, Uchimura K, Shiraishi
N, Miyoshi T, Adachi M, Aritomi S, Konda T, Tomita K,
Kitamura K. Regulation of adrenal aldosterone production by
serine
protease
prostasin.
J
Biomed
Biotechnol.
2010;2010:793843
Myerburg MM, McKenna EE, Luke CJ, Frizzell RA, Kleyman
TR, Pilewski JM. Prostasin expression is regulated by airway
surface liquid volume and is increased in cystic fibrosis. Am J
Physiol Lung Cell Mol Physiol. 2008 May;294(5):L932-41
Li K, Guo D, Zhu H, Hering-Smith KS, Hamm LL, Ouyang J,
Dong Y. Interleukin-6 stimulates epithelial sodium channels in
mouse cortical collecting duct cells. Am J Physiol Regul Integr
Comp Physiol. 2010 Aug;299(2):R590-5
Zhu H, Guo D, Li K, Yan W, Tan Y, Wang X, Treiber FA, Chao
J, Snieder H, Dong Y. Prostasin: a possible candidate gene for
human hypertension. Am J Hypertens. 2008 Sep;21(9):102833
Spacek DV, Perez AF, Ferranti KM, Wu LK, Moy DM, Magnan
DR, King TR. The mouse frizzy (fr) and rat 'hairless' (frCR)
mutations are natural variants of protease serine S1 family
member 8 (Prss8). Exp Dermatol. 2010 Jun;19(6):527-32
Chen LM, Hatfield ML, Fu YY, Chai KX. Prostasin regulates
iNOS and cyclin D1 expression by modulating proteaseactivated receptor-2 signaling in prostate epithelial cells.
Prostate. 2009a Dec 1;69(16):1790-801
Steensgaard M, Svenningsen P, Tinning AR, Nielsen TD,
Jørgensen F, Kjaersgaard G, Madsen K, Jensen BL. Apical
serine protease activity is necessary for assembly of a highresistance renal collecting duct epithelium. Acta Physiol (Oxf).
2010 Dec;200(4):347-59
Chen LM, Verity NJ, Chai KX. Loss of prostasin (PRSS8) in
human bladder transitional cell carcinoma cell lines is
associated with epithelial-mesenchymal transition (EMT). BMC
Cancer. 2009b Oct 22;9:377
Coote K, Atherton-Watson HC, Sugar R, Young A, MacKenzieBeevor A, Gosling M, Bhalay G, Bloomfield G, Dunstan A,
Bridges RJ, Sabater JR, Abraham WM, Tully D, Pacoma R,
Schumacher A, Harris J, Danahay H. Camostat attenuates
airway epithelial sodium channel function in vivo through the
inhibition of a channel-activating protease. J Pharmacol Exp
Ther. 2009 May;329(2):764-74
Frateschi S, Camerer E, Crisante G, Rieser S, Membrez M,
Charles RP, Beermann F, Stehle JC, Breiden B, Sandhoff K,
Rotman S, Haftek M, Wilson A, Ryser S, Steinhoff M, Coughlin
SR, Hummler E. PAR2 absence completely rescues
inflammation and ichthyosis caused by altered CAP1/Prss8
expression in mouse skin. Nat Commun. 2011 Jan 18;2:161
Friis S, Godiksen S, Bornholdt J, Selzer-Plon J, Rasmussen
HB, Bugge TH, Lin CY, Vogel LK. Transport via the
transcytotic pathway makes prostasin available as a substrate
for matriptase. J Biol Chem. 2011 Feb 18;286(7):5793-802
Koda A, Wakida N, Toriyama K, Yamamoto K, Iijima H, Tomita
K, Kitamura K. Urinary prostasin in humans: relationships
among prostasin, aldosterone and epithelial sodium channel
activity. Hypertens Res. 2009 Apr;32(4):276-81
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(9)
663
PRSS8 (protease, serine, 8)
Chen LM, Chai KX
Li NF, Zhang JH, Chang JH, Yang J, Wang HM, Zhou L, Luo
WL. Association of genetic variations of the prostasin gene
with essential hypertension in the Xinjiang Kazakh population.
Chin Med J (Engl). 2011 Jul;124(14):2107-12
Bergum C, Zoratti G, Boerner J, List K. Strong expression
association between matriptase and its substrate prostasin in
breast cancer. J Cell Physiol. 2012 Apr;227(4):1604-9
This article should be referenced as such:
Yip P, Chen TH, Seshaiah P, Stephen LL, Michael-Ballard KL,
Mapes JP, Mansfield BC, Bertenshaw GP. Comprehensive
serum profiling for the discovery of epithelial ovarian cancer
biomarkers. PLoS One. 2011;6(12):e29533
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(9)
Chen LM, Chai KX. PRSS8 (protease, serine, 8). Atlas Genet
Cytogenet Oncol Haematol. 2012; 16(9):658-664.
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