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AgnieszkaSzymczyk,EwaForma
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of5exonsand4intronsandresidesonchromosome13q12.TheαKlothogene
encodesasingle-passtransmembraneproteinwhichinhumanisprimarily
expressedinthekidney.Moreover,thelowerexpressionofαKLwasdetected
inmanyothertissues,suchasthepituitarygland,brain,parathyroidgland,
pancreas,ovary,testis,placenta,skeletalmuscle,urinarybladder,colon,inner
earandbreastepithelialcells[3].ThetransmembraneformofKlothoproteinhas
1012aminoacidsanditiscomposedofalargeextracellulardomain(~960aa),
atransmembranedomain(21aa),andaveryshortintracellulardomain(11aa).
Theextracellulardomainconsistsoftwointernalsof440aminoacidsrepeat
sequencesnamedKL1andKL2whichhavetheenzymaticactivity[4].
TheextracellulardomainofKlothoproteincanbecleavedbythemembersof
theADesintegrinandMetalloproteinase(ADAM)familyi.e.ADAM10and
ADAM17,thenKlothocanbereleasedfromthecellmembrane.Thesecreted
formofKlothowhichconsistsofthefull-lengthextracellulardomainisdetected
intheblood,urine,andcerebrospinalfluid[3-5].ThesecretedformofKlotho
canbealsogeneratedbyalternativemRNAsplicinginthethirdexon,andthen
containsonlyKL1domain[3].ThisformofKlothoproteinwasdetectedonly
intourine[4].Klothoproteincanregulatevariousmetabolicprocesses.
ThemembraneformofKlothofunctionsasanobligatoryco-receptorfor
endocrinefibroblastgrowthfactor23(FGF23)andregulatesphosphateand
vitaminDhomeostasis[2,3].RecentlyithasalsobeenfoundthatKlothoprotein
wouldinhibitFGF/FGFRsignalingpathwaydependonFGF8andprobably
otherparacrinesubfamilyligands[6].ThesecretedformofKlothoproteincan
regulatetheactivityofmultipleionchannelsandgrowthfactorsincluding
insulin,IGF-1,andWnt[2,3].
TheaberrantexpressionofαKLwasfoundinseveraltypesofcancer.
Moreover,inmostofthesecancersαKlothofunctionsasatumorsuppressor.
Itisproposedthattwomechanismsunderlyingthedecreaseexpression
ofKlotho,arethehypermethylationofKlothopromoter,anddeacetylation
ofhistonesattachedtothepromoter[7].
Bladdercancer(BCa)isthemostcommoncanceroftheurinarytract
inPolishpopulation.Thisisthefourthmostfrequentcancer(afterlungcancer,
prostateandcoloncancers)inmenandthethirteenthinwomen.Moreover,
bladdercanceristhefifthmostcommoncauseofcancerdeathsinmen[8].
