CYR61

S Wikipedije, slobodne enciklopedije
CYR61
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

4D0Z, 4D11

Identifikatori
AliasiCCN1
Vanjski ID-jeviOMIM: 602369 MGI: 88613 HomoloGene: 1194 GeneCards: CCN1
Lokacija gena (čovjek)
Hromosom 1 (čovjek)
Hrom.Hromosom 1 (čovjek)[1]
Hromosom 1 (čovjek)
Genomska lokacija za CYR61
Genomska lokacija za CYR61
Bend1p22.3Početak85,580,761 bp[1]
Kraj85,584,589 bp[1]
Lokacija gena (miš)
Hromosom 3 (miš)
Hrom.Hromosom 3 (miš)[2]
Hromosom 3 (miš)
Genomska lokacija za CYR61
Genomska lokacija za CYR61
Bend3 H2|3 70.18 cMPočetak145,352,731 bp[2]
Kraj145,355,736 bp[2]
Obrazac RNK ekspresije


Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• insulin-like growth factor binding
• growth factor binding
• extracellular matrix binding
• integrin binding
• heparin binding
• extracellular matrix structural constituent
Ćelijska komponenta• GO:0005578 Vanćelijski matriks
• extracellular region
• Vanćelijsko
• endoplasmic reticulum lumen
• collagen-containing extracellular matrix
Biološki proces• positive regulation of osteoblast proliferation
• apoptotic process involved in heart morphogenesis
• positive regulation of ceramide biosynthetic process
• positive regulation of protein phosphorylation
• ventricular septum development
• positive regulation of cell migration
• anatomical structure morphogenesis
• extracellular matrix organization
• negative regulation of apoptotic process
• labyrinthine layer blood vessel development
• reactive oxygen species metabolic process
• chorio-allantoic fusion
• chondroblast differentiation
• Hemotaksija
• positive regulation of phospholipase activity
• atrial septum morphogenesis
• positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
• intussusceptive angiogenesis
• positive regulation of osteoblast differentiation
• atrioventricular valve morphogenesis
• positive regulation of cartilage development
• regulation of cell growth
• osteoblast differentiation
• positive regulation of cell differentiation
• regulation of ERK1 and ERK2 cascade
• positive regulation of BMP signaling pathway
• positive regulation of apoptotic process
• Ćelijska proliferacija
• wound healing, spreading of cells
• GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
• positive regulation of protein kinase activity
• positive regulation of cell-substrate adhesion
• Posttranslacione modifikacije
• Ćelijska adhezija
• cell-cell signaling
• negative regulation of cell death
• cell-cell adhesion
• positive regulation of bone mineralization
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

3491

16007

Ensembl

ENSG00000142871

ENSMUSG00000028195

UniProt

O00622

P18406

RefSeq (mRNK)

NM_001554

NM_010516

RefSeq (bjelančevina)

NP_001545

NP_034646

Lokacija (UCSC)Chr 1: 85.58 – 85.58 MbChr 3: 145.35 – 145.36 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Cisteinom bogati angiogeni induktor 61 (CYR61) ili član 1 porodice proteina CCN (CCN1), jest matrićelijski protein koji je kod ljudi kodiran genom CYR61 sa hromosoma 1.[5]

CYR61 je izlučeni, vanćelijskomatriksni (ECM)-vezan signalni protein iz CCN porodice (unutarćelijski signalni protein CCN).[6][7] CYR61 je sposoban da reguliše širok spektar ćelijskih aktivnosti, uključujući ćelijsku adheziju, migraciju, proliferaciju, diferencijaciju, apoptozu i starenje putem interakcije sa integrinskim receptorima na površini ćelije i heparan-sulfatnim proteoglikanima. Tokom embrionskog razvoja, CYR61 je kritičan za morfogenezu srčanog septuma, formiranje krvnih sudova u placenti i vaskularni integritet. U odrasloj dobi, CYR61 ima važnu ulogu u upalama i obnavljanju tkiva, a u vezi je s bolestima povezanim s hroničnom upalom, uključujući reumatoidni artritis, aterosklerozu, dijabetes povezanu nefropatiju i retinopatiju, te mnoge različite oblike kancera.

CCN porodica proteina[uredi | uredi izvor]

CYR61 je prvi put identificiran kao protein kodiran genom koji se inducira u serumu u fibroblastima miša.[6][8] Kasnije su identifikovani i drugi visoko konzervirani homolozi, koji obuhvataju porodicu proteina CCN (CCN unutarćelijski signalni protein).[9][10][11] CCN akronim je izveden od prva tri identifikovana člana porodice, CYR61 (CCN1), CTGF (faktor rasta vezivnog tkiva ili CCN2) i NOV (preeksprimirani nefroblastom ili CCN3). Ovi proteini, zajedno sa WISP1 (CCN4), WISP2 (CCN5) i WISP3 (CCN6) čine šest članova kičmenjačke porodice i preimenovani su, međunarodnim konsenzusom, u CCN1-6 po redu njihovog otkrića.[12] CCN proteini funkcionišu kao matrićelijskii proteini, proteini vanćelijskog matriksa koji imaju regulatorne uloge, posebno u kontekstu zacjeljivanja rana.[13]

Amiokiselininska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 381 aminokiselina, a molekulska težina 42.027 Da.[14]

1020304050
MSSRIARALALVVTLLHLTRLALSTCPAACHCPLEAPKCAPGVGLVRDGC
GCCKVCAKQLNEDCSKTQPCDHTKGLECNFGASSTALKGICRAQSEGRPC
EYNSRIYQNGESFQPNCKHQCTCIDGAVGCIPLCPQELSLPNLGCPNPRL
VKVTGQCCEEWVCDEDSIKDPMEDQDGLLGKELGFDASEVELTRNNELIA
VGKGSSLKRLPVFGMEPRILYNPLQGQKCIVQTTSWSQCSKTCGTGISTR
VTNDNPECRLVKETRICEVRPCGQPVYSSLKKGKKCSKTKKSPEPVRFTY
AGCLSVKKYRPKYCGSCVDGRCCTPQLTRTVKMRFRCEDGETFSKNVMMI
QSCKCNYNCPHANEAAFPFYRLFNDIHKFRD

Struktura i regulacija gena[uredi | uredi izvor]

CYR61 se nalazi na ljudskom hromosomu 1, regija p22.3, dok se gen Cyr61 miša nalazi na hromosomu 3, 72.9cM.[15] Kodirajuća regija mišjeg CYR61 prostire se na ~3,2 Kb i sadrži pet međuprostornih egzona sa četiri introna.[16] Prvi egzon kodira sekvencu 5' UTR i prvih nekoliko aminokiselina u sekretornom signalnom peptidu. Preostala četiri egzona kodiraju različit CCN1 domen. Peti egzon također sadrži sekvencu 3' UTR, koja ima pet kopija AU-bogatih elermenata koji daje kratkopoluživotnu iRNK i mir-155 ciljnu lokaciju.[17] Promotor CYR61 je TATA-kutija koja sadrži promotor, sa veznim mjestima za mnoge transkripcijske faktore uključujući AP1, ATF, E2F, HNF3b, NF1, NFκB, SP1 i SRF i dva poli(CA) dijela koji mogu formirati Z-DNK strukturu. Transkripcijska aktivacija CYR61 je izuzetno osjetljiva na širok spektar perturbacija okoline, uključujući stimulaciju trombocitni faktor rasta i osnovni faktor rasta fibroblasta, transformirajući faktor rasta β1 (TGF-β1) , hormon rasta, forbol-ester 12-O-tetradekanoilforbol-13-acetat (TPA), cAMP, vitamin D3, estrogen i tamoksifen, angiotenzin II, hipoksiju, UV svjetlo i mehaničko rastezanje.[7][11]

Proteinska struktura i funkcija[uredi | uredi izvor]

Strukturni domeni[uredi | uredi izvor]

CYR61 protein pune dužine sadrži 381 aminokiselinu sa N-terminalnim sekretornim signalnim peptidom, nakon čega slijede četiri strukturno različita domena.[18] Četiri domena CYR61 su, od N– do C-kraja, domen proteina koji vezuje faktor rasta nalik insulinu (IGFBP), von Willebrandov tip C-ponavljanja vWC domena, trombospondin tip 1 ponavljanja domena (TSR) i C-terminalni (CT) domen koji sadrži motiv cisteinskog čvora. CCN1 ima neobično visok sadržaj cisteinskih ostataka (10% ili 38 ukupno). Broj i razmak cisteinskih ostataka potpuno su konzervirano među CYR61 (CCN1), CTGF (CCN2), NOV (CCN3) i WISP-1 (CCN4), a u velikoj mjeri konzervirani su kod WISP-2 (CCN5), kojem nedostaje upravo CT domen i WISP3 (CCN6), kojem nedostaju četiri cisteina u vWC domenu. CYR61 je glikoziliran, iako su regulacija i funkcija gilkozilacije nepoznati.

Struktura proteina CCN1

Vezanje integrina[uredi | uredi izvor]

CYR61 se direktno vezuje za različite integrinske receptore na način ovisan o tipu ćelije, uključujući integrin αvβ3 u endotelnim ćelijama,[19] α6β1 i heparan-sulfatne proteoglikane (HSPGs) u fibroblastima i ćelijama glatkih mišića .[20][21] αIIbβ3 u aktiviranim trombocitima,[22] αMβ2 u monocitima i makrofagima,[23][24] i αDβ2 u pjenastim ćelijama makrofaga.[25] Kada je ispitan, sindekan-4 je identificiran kao HSPG kritičan za funkcije CCN1.[26][27] Mjesta vezanja CYR61 za neke od ovih integrina su mapirana (Slika 1). Zbog specifičnosti ćelijskog tipa ekspresije integrina, CYR61 djeluje kroz različite integrine, kako bi posredovao u specifičnim funkcijama u različitim tipovima ćelija. Na primjer, CYR61 inducira angiogene funkcije u endotelnim ćelijama putem αvβ3,[28] a u fibroblastima podstiče ćelijsko starenje i omogućava TNFα da indukuje apoptozu, vezivanjem za α6β1-HSPGs.[27][29] Međutim, CYR61 podržava ćelijsku adheziju putem svih gore identificiranih integrina.

Ćelijska signalizacija i funkcija[uredi | uredi izvor]

Kao ćelijski adhezivni supstrat, CYR61 inducira aktivaciju fokusne adhezijske kinaze, paksilina, RAC i trajnu aktivaciju MAPK/ERK1-2.[30] U makrofagima, CYR61 također aktivira transkripcijski faktor NFκB i stimulira polarizaciju M1.[24] CYR61 aktivira Akt signalizaciju u epitelnim ćelijama timusa, promovirajući njihovu proliferaciju i time rast veličine timusa.[31] CYR61 ima snažnu angiogenu aktivnost na endotelne ćelije i inducira neovaskularizaciju, što je prvi put pokazano u testu mikrodžepova implantata rožnjače [32] i naknadno potvrđeno na modelu kunićne ishemije stražnjeg mozga.[33] CYR61 također ubrzava i podstiče hondrogenu diferencijaciju mezenhimskih ćelijaa pupoljaka mišjih ekstremiteta,[34] i stimulira diferencijaciju osteoblasta, ali inhibira osteoklastogenezu.[35][36][37] Cyr61 je snažan induktor akumulacije reaktivnih vrsta kisika u fibroblastnim ćelijama, a ova aktivnost je u osnovi mnogih CYR61 induciranih apoptoza i starenja.[27][29] CYR61 je u stanju podržati ćelijsku adheziju, stimulira migraciju ćelija, promovira proliferaciju i diferencijaciju ćelija izazvanu faktorom rasta u nekim tipovima ćelija, promovira apoptozu u sinergiji sa citokinima porodice TNF i inducira ćelijsko starenje u fibroblastima.

Embrionalni razvoj[uredi | uredi izvor]

Tokom razvoja embriona kod miševa, "Cyr61" je visoko eksprimiran u kardiovaskularnom, skeletnom i neuronskom sistemu.[38][39] Cyr61 nokaut-miševa su embrionalno smrtonosni zbog defekata u morfogenezi srčanog septuma, manjkavog formiranja krvnih sudova u placenti i ugroženog vaskularnog integriteta.[40][41] Kod Xenopus laevis, Cyr61 je potreban za normalnu gastrulaciju i modulaciju Wnt-signalizaciju.[42]

Klinički značaj[uredi | uredi izvor]

CYR61 je visoko eksprimiran na mjestima upale i popravke rana, a povezan je s bolestima koje uključuju hroničnu upalu i ozljedu tkiva.[7]

Zacjeljivanje rana i fibroza[uredi | uredi izvor]

U kožnon zacjeljivanju rana, CYR61 je visoko eksprimiran u granulastom tkivu pomoću miofibroblasta, koji proliferiraju i brzo sintetiziraju ECM, kako bi održali integritet tkiva i promovirali regeneraciju parenhimskih ćelija.[43][44] Međutim, prekomjerno taloženje matriksa može dovesti do fibroze, ožiljaka i gubitka funkcije tkiva. U ranama na koži, CYR61 se akumulira u granulastom tkivu, kako miofibroblasti proliferiraju i na kraju dostiže dovoljno visok nivo da dovede do starenja same miofibroblaste, nakon čega ove ćelije prestaju da se razmnožavaju i eksprimiraju enzime koji razgrađuju matriks.[29] Dakle, CYR61 ograničava sintezu i taloženje ECM putem miofibroblasta, smanjujući rizik od fibroze tokom zarastanja rana.[45] Osim zacjeljivanja rana na koži, ekspresija CYR61 je povišena u remodeliranju kardiomiocita nakon infarkta miokarda,[46] kod vaskularnih ozljeda,[21] i kod dugih kostiju tokom sanacije prijeloma.[47][48] Blokada CYR61 antitelima inhibira zarastanje prijeloma kostiju kod miševa.[49] U bubrezima, CYR61 se eksprimira u podocitima u normalnim odraslim i embrionalnim glomerulima, ali je ekspresija smanjena u IgA-nefropatijama, dijabeteskoj i membranoznoj nefropatiji, posebno u bolesnim bubrezima s teškim mezangijnim ekspanzijama.[50] CYR61 indukcija ćelijskog starenja u bubrezima potencijalna je terapija za ograničavanje fibroze.[51]

Upala[uredi | uredi izvor]

CYR61 promovira apoptotske funkcije upalnih citokina kao što su TNFα, FasL i TRAIL.[27][52][53] Također reprogramira makrofage prema M1 polarizaciji preko αMβ2 posredovane aktivacije NF-κB.[24] CYR61 je pojačan kod pacijenata sa Crohnovom bolešću i ulceroznim kolitisom.[54] CYR61 podržava ponašanje patroliranja mišjih rezidentnih Ly6Cniskih monocita duž endotela u stabilnom stanju i potreban je za njihovu akumulaciju pod vaskularnom upalom koja oponaša virus.[55]

Artritis[uredi | uredi izvor]

CYR61 je visoko eksprimiran u artritisu izazvanom kolagenom kod glodara, a inhibicija ekspresije CCN1 korelira sa supresijom upalnog artritisa.[56] CYR61 se također nalazi u zglobnoj hrskavici pacijenata s osteoartritisom i čini se da potiskuje aktivnost ADAMTS4 (agrekanaze), što može dovesti do kloniranja ćelija hrskavica (hondrocita)..[57]

Vaskularne bolesti[uredi | uredi izvor]

CYR61 je prekomjerno eksprimiran u ćelijama vaskularnih glatkih mišića, aterosklerotskih lezija i u restenozama noointime nakon balonske angioplastike, kako kod modela glodra, tako i kod ljudi.[21][23][58][59] Supresija ekspresije CYR61 rezultira smanjenom neointimnom hiperplazijom nakon balonske angioplastike, efekt koji se poništava isporukom CYR61 putem prijenosa gena[60][61] Na mišjem modelu retinopatije izazvane kisikom, ekspresija CYR61 u staklastom tijelu dala je značajne korisne efekte u popravljanju oštećene vaskulature.[62]

Kancer[uredi | uredi izvor]

Za opskrbu kisikom i hranjivim tvarima za ishranu rastućeg tumora, neophodna je angiogeneza.[63] CYR61 je snažan angiogeni induktor in vivo,[32][33] i također može promovirati proliferaciju ćelija raka, invaziju, preživljavanje, epitelno-mezenhimalni prijelaz i metastaze.[64][65][66][67] Shodno tome, prisilna prekomjerna ekspresija CYR61 pojačala je rast tumora u ksenotransplantatnim ćelijama raka dojke,[68] prostate,[65] ćelijama raka jajnika[69] ćelijama raka pločastih ćelija.[70] Klinički, ekspresija CYR61 korelira sa stadijem i veličinom tumora, pozitivnošću limfnih čvorova i lošom prognozom kod nekoliko karcinoma, uključujući rak dojke,[68][71][72][73][74] rak prostate,[75] gliom,[76] želučani adenokarcinom[77] i karcinom skvamoznih ćelija.[70]

Međutim, CYR61 također može izazvati apoptoze[] i ćelijsko starenje,[26][29][78] dva dobro uspostavljena mehanizma supresije tumora.[79] Dakle, dok CYR61 može promovirati proliferaciju ćelija raka prostate, on također može pogoršati njihovu apoptozu u prisustvu molekula imunoskog nadzora TRAIL.[53][65][80] CYR61 ima inhibitorni efekat na neke tipove raka i potiskuje rast tumorskih ćelija nemaloćelijskog karcinoma pluća (NSCLC),[81] ćelija endometrijskog adenokarcinoma,[82] i u ćelijama melanoma.[83]

Reference[uredi | uredi izvor]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000142871 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028195 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Jay P, Berge-Lefranc JL, Marsollier C, Mejean C, Taviaux S, Berta P (maj 1997). "The human growth factor-inducible immediate early gene, CYR61, maps to chromosome 1p". Oncogene. 14 (14): 1753–7. doi:10.1038/sj.onc.1200986. PMID 9135077.
  6. ^ a b Lau LF (oktobar 2011). "CCN1/CYR61: the very model of a modern matricellular protein". Cell. Mol. Life Sci. 68 (19): 3149–63. doi:10.1007/s00018-011-0778-3. PMC 3651699. PMID 21805345.
  7. ^ a b c Jun JI, Lau LF (decembar 2011). "Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets". Nature Reviews Drug Discovery. 10 (12): 945–63. doi:10.1038/nrd3599. PMC 3663145. PMID 22129992.
  8. ^ Lau LF, Nathans D (1985). "Identification of a set of genes expressed during the G0/G1 transition of cultured mouse cells". EMBO J. 4 (12): 3145–3151. doi:10.1002/j.1460-2075.1985.tb04057.x. PMC 554634. PMID 3841511.
  9. ^ Leask A, Abraham DJ (2006). "All in the CCN family: essential matricellular signaling modulators emerge from the bunker". J. Cell Sci. 119 (Pt 23): 4803–4810. doi:10.1242/jcs.03270. PMID 17130294.
  10. ^ Holbourn KP, Acharya KR, Perbal B (2008). "The CCN family of proteins: structure-function relationships". Trends Biochem. Sci. 33 (10): 461–473. doi:10.1016/j.tibs.2008.07.006. PMC 2683937. PMID 18789696.
  11. ^ a b Chen CC, Lau LF (2009). "Functions and Mechanisms of Action of CCN Matricellular Proteins". Int. J. Biochem. Cell Biol. 41 (4): 771–783. doi:10.1016/j.biocel.2008.07.025. PMC 2668982. PMID 18775791.
  12. ^ Brigstock DR, Goldschmeding R, Katsube KI, Lam SC, Lau LF, Lyons K, Naus C, Perbal B, Riser B (2003). "Proposal for a unified CCN nomenclature". Mol. Pathol. 56 (2): 127–128. doi:10.1136/mp.56.2.127. PMC 1187305. PMID 12665631.
  13. ^ Bornstein P, Sage EH (2002). "Matricellular proteins: extracellular modulators of cell function". Current Opinion in Cell Biology. 14 (5): 608–616. doi:10.1016/S0955-0674(02)00361-7. PMID 12231357.
  14. ^ "UniProt, O00622" (jezik: engleski). Pristupljeno 23. 11. 2021.
  15. ^ Jay P, Berge-Lefranc JL, Marsollier C, Mejean C, Taviaux S, Berta P (1997). "The human growth factor-inducible immediate early gene, CYR61, maps to chromosome 1p". Oncogene. 14 (14): 1753–1757. doi:10.1038/sj.onc.1200986. PMID 9135077.
  16. ^ Latinkic BV, O'Brien TP, Lau LF (1991). "Promoter function and structure of the growth factor-inducible immediate early gene cyr61". Nucleic Acids Res. 19 (12): 3261–3267. doi:10.1093/nar/19.12.3261. PMC 328320. PMID 2062642.
  17. ^ Zhang Y, Diao Z, Su L, Sun H, Li R, Cui H, Hu Y (2010). "MicroRNA-155 contributes to preeclampsia by down-regulating CYR61". Am. J. Obstet. Gynecol. 202 (5): 466–467. doi:10.1016/j.ajog.2010.01.057. PMID 20452491.
  18. ^ O'Brien TP, Yang GP, Sanders L, Lau LF (1990). "Expression of cyr61, a growth factor-inducible immediate-early gene". Mol. Cell. Biol. 10 (7): 3569–3577. doi:10.1128/MCB.10.7.3569. PMC 360792. PMID 2355916.
  19. ^ Kireeva ML, Lam SC, Lau LF (1998). "Adhesion of human umbilical vein endothelial cells to the immediate-early gene product Cyr61 is mediated through integrin αvβ3". J. Biol. Chem. 273 (5): 3090–3096. doi:10.1074/jbc.273.5.3090. PMID 9446626.
  20. ^ Chen N, Chen CC, Lau LF (2000). "Adhesion of human skin fibroblasts to Cyr61 is mediated through integrin α6β1 and cell surface heparan sulfate proteoglycans". J. Biol. Chem. 275 (32): 24953–24961. doi:10.1074/jbc.M003040200. PMID 10821835.
  21. ^ a b c Grzeszkiewicz TM, Lindner V, Chen N, Lam SC, Lau LF (2002). "The angiogenic factor CYR61 supports vascular smooth muscle cell adhesion and stimulates chemotaxis through integrin α6β1 and cell surface heparan sulfate proteoglycans". Endocrinology. 143 (4): 1441–1450. doi:10.1210/en.143.4.1441. PMID 11897702.
  22. ^ Jedsadayanmata A, Chen CC, Kireeva ML, Lau LF, Lam SC (1999). "Activation-dependent adhesion of human platelets to Cyr61 and Fisp12/Mouse connective tissue growth factor is mediated through integrin αIIbβ3". J. Biol. Chem. 274 (34): 24321–24327. doi:10.1074/jbc.274.34.24321. PMID 10446209.
  23. ^ a b Schober JM, Chen N, Grzeszkiewicz TM, Emeson EE, Ugarova TP, Ye RD, Lau LF, Lam SC, Lam SC (2002). "Identification of integrin αMβ2 as an adhesion receptor on peripheral blood moncytes for Cyr61 (CCN1) and connective tissue growth factor (CCN2), immediate-early gene products expressed in atherosclerotic lesions". Blood. 99 (12): 4457–4465. doi:10.1182/blood.V99.12.4457. PMID 12036876.
  24. ^ a b c Bai T, Chen CC, Lau LF (2010). "The matricellular protein CCN1 activates a pro-inflammatory genetic program in murine macrophages". J. Immunol. 184 (6): 3223–3232. doi:10.4049/jimmunol.0902792. PMC 2832719. PMID 20164416.
  25. ^ Yakubenko VP, Yadav SP, Ugarova TP (2006). "Integrin αDβ2, an adhesion receptor up-regulated on macrophage foam cells, exhibits multiligand-binding properties". Blood. 107 (4): 1643–1650. doi:10.1182/blood-2005-06-2509. PMC 1367263. PMID 16239428.
  26. ^ a b Todorovic V, Chen CC, Hay N, Lau LF (2005). "The matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts". J. Cell Biol. 171 (3): 559–568. doi:10.1083/jcb.200504015. PMC 1626352. PMID 16275757.
  27. ^ a b c d Chen CC, Young JL, Monzon RI, Chen N, Todorovic V, Lau LF (2007). "Cytotoxicity of TNFα is regulated by Integrin-Mediated Matrix Signaling". EMBO J. 26 (5): 1257–1267. doi:10.1038/sj.emboj.7601596. PMC 1817641. PMID 17318182.
  28. ^ Leu SJ, Lam SC, Lau LF (2002). "Proangiogenic activities of CYR61 (CCN1) mediated through integrins αvβ3 and α6β1 in human umbilical vein endothelial cells". J. Biol. Chem. 277 (48): 46248–46255. doi:10.1074/jbc.M209288200. PMID 12364323.
  29. ^ a b c d Jun JI, Lau LF (2010). "The Matricellular Protein CCN1/CYR61 Induces Fibroblast Senescence and Restricts Fibrosis in Cutaneous Wound Healing". Nat. Cell Biol. 12 (7): 676–685. doi:10.1038/ncb2070. PMC 2919364. PMID 20526329.
  30. ^ Chen CC, Chen N, Lau LF (2001). "The angiogenic factors Cyr61 and CTGF induce adhesive signaling in primary human skin fibroblasts". J. Biol. Chem. 276 (13): 10443–10452. doi:10.1074/jbc.M008087200. PMID 11120741.
  31. ^ Emre, Yalin; Irla, Magali; Dunand-Sauthier, Isabelle; Ballet, Romain; Meguenani, Mehdi; Jemelin, Stephane; Vesin, Christian; Reith, Walter; Imhof, Beat A. (27. 11. 2013). "Thymic epithelial cell expansion through matricellular protein CYR61 boosts progenitor homing and T-cell output". Nature Communications (jezik: engleski). 4: 2842. Bibcode:2013NatCo...4.2842E. doi:10.1038/ncomms3842. PMID 24280864.
  32. ^ a b Babic AM, Kireeva ML, Kolesnikova TV, Lau LF (1998). "CYR61, product of a growth factor-inducible immediate-early gene, promotes angiogenesis and tumor growth". Proc. Natl. Acad. Sci. U.S.A. 95 (11): 6355–6360. Bibcode:1998PNAS...95.6355B. doi:10.1073/pnas.95.11.6355. PMC 27701. PMID 9600969.
  33. ^ a b Fataccioli V, Abergel V, Wingertsmann L, Neuville P, Spitz E, Adnot S, Calenda V, Teiger E (2002). "Stimulation of angiogenesis by cyr61 gene: a new therapeutic candidate". Hum. Gene Ther. 13 (12): 1461–1470. doi:10.1089/10430340260185094. PMID 12215267.
  34. ^ Wong M, Kireeva ML, Kolesnikova TV, Lau LF (1997). "Cyr61, product of a growth factor-inducible immediate-early gene, regulates chondrogenesis in mouse limb bud mesenchymal cells". Dev. Biol. 192 (2): 492–508. doi:10.1006/dbio.1997.8766. PMID 9441684.
  35. ^ Si W, Kang Q, Luu HH, Park JK, Luo Q, Song WX, Jiang W, Luo X, Li X (2006). "CCN1/Cyr61 is regulated by the canonical Wnt signal and plays an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells". Mol. Cell. Biol. 26 (8): 2955–2964. doi:10.1128/MCB.26.8.2955-2964.2006. PMC 1446962. PMID 16581771.
  36. ^ Crockett JC, Schutze N, Tosh D, Jatzke S, Duthie A, Jakob F, Rogers MJ (2007). "The matricellular protein CYR61 inhibits osteoclastogenesis by a mechanism independent of αvβ3 and αvβ5". Endocrinology. 148 (12): 5761–5768. doi:10.1210/en.2007-0473. PMID 17823253.
  37. ^ Su JL, Chiou J, Tang CH, Zhao M, Tsai CH, Chen PS, Chang YW, Chien MH, Peng CY (2010). "CYR61 regulates BMP-2-dependent osteoblast differentiation through the αvβ3 integrin/integrin-linked kinase/ERK pathway". J. Biol. Chem. 285 (41): 31325–31336. doi:10.1074/jbc.M109.087122. PMC 2951207. PMID 20675382.
  38. ^ O'Brian TP, Lau LF (1992). "Expression of the Growth Factor-Inducible Immediate Early Gene cyr61 Correlates with Chondrogenesis During Mouse Embryonic Development". Cell Growth & Differentiation. 3 (9): 645–654. PMID 1419914.
  39. ^ Latinkic BV, Mo FE, Greenspan JA, Copeland NG, Gilbert DJ, Jenkins NA, Ross SR, Lau LF (2001). "Promoter Function of the Angiogenic Inducer Cyr61 Gene in Transgenic Mice: Tissue Specificity, Inducibility During Wound Healing, and Role of the Serum Response Element". Endocrinology. 142 (6): 2549–2557. doi:10.1210/en.142.6.2549. PMID 11356704.
  40. ^ Mo FE, Muntean AG, Chen CC, Stolz DB, Watkins SC, Lau LF (2002). "CYR61 (CCN1) Is Essential for Placental Development and Vascular Integrity". Mol. Cell. Biol. 22 (24): 8709–8720. doi:10.1128/MCB.22.24.8709-8720.2002. PMC 139880. PMID 12446788.
  41. ^ Mo FE, Lau LF (2006). "The matricellular protein CCN1 is essential for cardiac development". Circ. Res. 99 (9): 961–969. doi:10.1161/01.RES.0000248426.35019.89. PMC 1626492. PMID 17023674.
  42. ^ Latinkic BV, Mercurio S, Bennett B, Hirst EM, Xu Q, Lau LF, Mohun TJ, Smith JC (2003). "Xenopus Cyr61 regulates gastrulation movements and modulates Wnt signalling". Development. 130 (11): 2429–2441. doi:10.1242/dev.00449. PMID 12702657.
  43. ^ Gurtner GC, Werner S, Barrandon Y, Longaker MT (2008). "Wound repair and regeneration". Nature. 453 (7193): 314–321. Bibcode:2008Natur.453..314G. doi:10.1038/nature07039. PMID 18480812. S2CID 205213660.
  44. ^ Wynn TA (2008). "Cellular and molecular mechanisms of fibrosis". The Journal of Pathology. 214 (2): 199–210. doi:10.1002/path.2277. PMC 2693329. PMID 18161745.
  45. ^ Jun JI, Lau LF (2010). "Cellular senescence controls fibrosis in wound healing". Aging. 2 (9): 627–631. doi:10.18632/aging.100201. PMC 2984611. PMID 20930261.
  46. ^ Hilfiker-Kleiner D, Kaminski K, Kaminska A, Fuchs M, Klein G, Podewski E, Grote K, Kiian I, Wollert KC (2004). "Regulation of proangiogenic factor CCN1 in cardiac muscle: impact of ischemia, pressure overload, and neurohumoral activation". Circulation. 109 (18): 2227–2233. doi:10.1161/01.CIR.0000127952.90508.9D. PMID 15117851.
  47. ^ Hadjiargyrou M, Ahrens W, Rubin CT (2000). "Temporal expression of the chondrogenic and angiogenic growth factor CYR61 during fracture repair". J. Bone Miner. Res. 15 (6): 1014–1023. doi:10.1359/jbmr.2000.15.6.1014. PMID 10841170.
  48. ^ Nakata E, Nakanishi T, Kawai A, Asaumi K, Yamaai T, Asano M, Nishida T, Mitani S, Inoue H (2002). "Expression of connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24) during fracture healing". Bone. 31 (4): 441–447. doi:10.1016/S8756-3282(02)00846-3. PMID 12398938.
  49. ^ Athanasopoulos AN, Schneider D, Keiper T, Alt V, Pendurthi UR, Liegibel UM, Sommer U, Nawroth PP, Kasperk C (2007). "Vascular endothelial growth factor (VEGF)-induced up-regulation of CCN1 in osteoblasts mediates proangiogenic activities in endothelial cells and promotes fracture healing". J. Biol. Chem. 282 (37): 26746–26753. doi:10.1074/jbc.M705200200. PMC 2831223. PMID 17626014.
  50. ^ Sawai K, Mukoyama M, Mori K, Kasahara M, Koshikawa M, Yokoi H, Yoshioka T, Ogawa Y, Sugawara A, Nishiyama H, Yamada S, Kuwahara T, Saleem MA, Shiota K, Ogawa O, Miyazato M, Kangawa K, Nakao K (oktobar 2007). "Expression of CCN1 (CYR61) in developing, normal, and diseased human kidney". Am. J. Physiol. Renal Physiol. 293 (4): F1363–72. doi:10.1152/ajprenal.00205.2007. PMID 17699553.
  51. ^ Valentijn FA, Falke LL, Nguyen TQ, Goldschmeding R (2018). "Cellular senescence in the aging and diseased kidney". Journal of Cell Communication and Signaling. 12 (1): 69–82. doi:10.1007/s12079-017-0434-2. PMC 5842195. PMID 29260442.
  52. ^ Juric V, Chen CC, Lau LF (2009). "Fas-Mediated Apoptosis is Regulated by the Extracellular Matrix Protein CCN1 (CYR61) in vitro and in vivo". Mol. Cell. Biol. 29 (12): 3266–3279. doi:10.1128/MCB.00064-09. PMC 2698731. PMID 19364818.
  53. ^ a b Franzen CA, Chen CC, Todorovic V, Juric V, Monzon RI, Lau LF (2009). "The Matrix Protein CCN1 is Critical for Prostate Carcinoma Cell Proliferation and TRAIL-Induced Apoptosis". Mol. Cancer Res. 7 (7): 1045–1055. doi:10.1158/1541-7786.MCR-09-0017. PMC 2712585. PMID 19584265.
  54. ^ Koon HW, Zhao D, Xu H, Bowe C, Moss A, Moyer MP, Pothoulakis C (2008). "Substance P-mediated expression of the pro-angiogenic factor CCN1 modulates the course of colitis". Am. J. Pathol. 173 (2): 400–410. doi:10.2353/ajpath.2008.080222. PMC 2475777. PMID 18599605.
  55. ^ Imhof, Beat A.; Jemelin, Stephane; Ballet, Romain; Vesin, Christian; Schapira, Marco; Karaca, Melis; Emre, Yalin (1. 8. 2016). "CCN1/CYR61-mediated meticulous patrolling by Ly6Clow monocytes fuels vascular inflammation". Proceedings of the National Academy of Sciences (jezik: engleski). 113 (33): E4847–E4856. doi:10.1073/pnas.1607710113. ISSN 0027-8424. PMC 4995973. PMID 27482114.
  56. ^ Kok SH, Hou KL, Hong CY, Wang JS, Liang PC, Chang CC, Hsiao M, Yang H, Lai EH, Lin SK (april 2011). "Simvastatin inhibits cytokine-stimulated Cyr61 expression in osteoblastic cells: a therapeutic benefit for arthritis". Arthritis Rheum. 63 (4): 1010–20. doi:10.1002/art.27433. PMID 20191585.
  57. ^ Chijiiwa M, Mochizuki S, Kimura T, Abe H, Tanaka Y, Fujii Y, Shimizu H, Enomoto H, Toyama Y, Okada Y (juni 2015). "CCN1 (Cyr61) Is Overexpressed in Human Osteoarthritic Cartilage and Inhibits ADAMTS-4 (Aggrecanase 1) Activity". Arthritis & Rheumatology. 67 (6): 1557–67. doi:10.1002/art.39078. PMID 25709087. S2CID 205431163.
  58. ^ Hilfiker A, Hilfiker-Kleiner D, Fuchs M, Kaminski K, Lichtenberg A, Rothkotter HJ, Schieffer B, Drexler H (2002). "Expression of CYR61, an angiogenic immediate early gene, in arteriosclerosis and its regulation by angiotensin II". Circulation. 106 (2): 254–260. doi:10.1161/01.CIR.0000021426.87274.62. PMID 12105167.
  59. ^ Sigala F, Georgopoulos S, Papalambros E, Chasiotis D, Vourliotakis G, Niforou A, Kotsinas A, Kavantzas N, Patsouris E (2006). "Heregulin, cysteine rich-61 and matrix metalloproteinase 9 expression in human carotid atherosclerotic plaques: relationship with clinical data". Eur. J. Vasc. Endovasc. Surg. 32 (3): 238–245. doi:10.1016/j.ejvs.2006.01.026. PMID 16774841.
  60. ^ Lee HY, Chung JW, Youn SW, Kim JY, Park KW, Koo BK, Oh BH, Park YB, Chaqour B (2007). "Forkhead transcription factor FOXO3a is a negative regulator of angiogenic immediate early gene CYR61, leading to inhibition of vascular smooth muscle cell proliferation and neointimal hyperplasia". Circ. Res. 100 (3): 372–380. doi:10.1161/01.RES.0000257945.97958.77. PMID 17234971.
  61. ^ Matsumae H, Yoshida Y, Ono K, Togi K, Inoue K, Furukawa Y, Nakashima Y, Kojima Y, Nobuyoshi M (2008). "CCN1 Knockdown Suppresses Neointimal Hyperplasia in a Rat Artery Balloon Injury Model". Arterioscler. Thromb. Vasc. Biol. 28 (6): 1077–1083. doi:10.1161/ATVBAHA.108.162362. PMID 18388330.
  62. ^ Hasan A, Pokeza N, Shaw L, Lee HS, Lazzaro D, Chintala H, Rosenbaum D, Grant MB, Chaqour B (mart 2011). "The matricellular protein cysteine-rich protein 61 (CCN1/Cyr61) enhances physiological adaptation of retinal vessels and reduces pathological neovascularization associated with ischemic retinopathy". J. Biol. Chem. 286 (11): 9542–54. doi:10.1074/jbc.M110.198689. PMC 3059032. PMID 21212276.
  63. ^ Folkman J (2006). "Angiogenesis". Annu. Rev. Med. 57: 1–18. doi:10.1146/annurev.med.57.121304.131306. PMID 16409133.
  64. ^ Monnier Y, Farmer P, Bieler G, Imaizumi N, Sengstag T, Alghisi GC, Stehle JC, Ciarloni L, Blant S (2008). "CYR61 and αVβ5 Integrin Cooperate to Promote Invasion and Metastasis of Tumors Growing in Preirradiated Stroma". Cancer Res. 68 (18): 7323–7331. doi:10.1158/0008-5472.CAN-08-0841. PMID 18794119.
  65. ^ a b c Sun ZJ, Wang Y, Cai Z, Chen PP, Tong XJ, Xie D (2008). "Involvement of Cyr61 in growth, migration, and metastasis of prostate cancer cells". Br. J. Cancer. 99 (10): 1656–1667. doi:10.1038/sj.bjc.6604712. PMC 2584944. PMID 18941464.
  66. ^ Kassis JN, Virador VM, Guancial EA, Kimm D, Ho AS, Mishra M, Chuang EY, Cook J, Gius D (2009). "Genomic and phenotypic analysis reveals a key role for CCN1 (CYR61) in BAG3-modulated adhesion and invasion". J. Pathol. 218 (4): 495–504. doi:10.1002/path.2557. PMC 7316387. PMID 19402132.
  67. ^ Haque I, Mehta S, Majumder M, Dhar K, De A, McGregor D, Van Veldhuizen PJ, Banerjee SK, Banerjee S (2011). "Cyr61/CCN1 signaling is critical for epithelial-mesenchymal transition and stemness and promotes pancreatic carcinogenesis". Mol. Cancer. 10: 8. doi:10.1186/1476-4598-10-8. PMC 3027193. PMID 21232118.
  68. ^ a b Xie D, Miller CW, O'Kelly J, Nakachi K, Sakashita A, Said JW, Gornbein J, Koeffler HP (2001). "Breast cancer. Cyr61 is overexpressed, estrogen-inducible, and associated with more advanced disease". J. Biol. Chem. 276 (17): 14187–14194. doi:10.1074/jbc.M009755200. PMID 11297518.
  69. ^ Gery S, Xie D, Yin D, Gabra H, Miller C, Wang H, Scott D, Yi WS, Popoviciu ML (2005). "Ovarian carcinomas: CCN genes are aberrantly expressed and CCN1 promotes proliferation of these cells". Clin. Cancer Res. 11 (20): 7243–7254. doi:10.1158/1078-0432.CCR-05-0231. PMID 16243794.
  70. ^ a b Kok SH, Chang HH, Tsai JY, Hung HC, Lin CY, Chiang CP, Liu CM, Kuo MY (2010). "Expression of Cyr61 (CCN1) in human oral squamous cell carcinoma: An independent marker for poor prognosis". Head Neck. 32 (12): 1665–1673. doi:10.1002/hed.21381. PMID 20848406. S2CID 42617874.
  71. ^ Tsai MS, Hornby AE, Lakins J, Lupu R (2000). "Expression and function of CYR61, an angiogenic factor, in breast cancer cell lines and tumor biopsies". Cancer Res. 60 (20): 5603–5607. PMID 11059746.
  72. ^ Xie D, Nakachi K, Wang H, Elashoff R, Koeffler HP (2001). "Elevated levels of connective tissue growth factor, WISP-1, and CYR61 in primary breast cancers associated with more advanced features". Cancer Res. 61 (24): 8917–8923. PMID 11751417.
  73. ^ Jiang WG, Watkins G, Fodstad O, Douglas-Jones A, Mokbel K, Mansel RE (2004). "Differential expression of the CCN family members Cyr61, CTGF and Nov in human breast cancer". Endocr. Relat. Cancer. 11 (4): 781–791. doi:10.1677/erc.1.00825. PMID 15613452.
  74. ^ O'Kelly J, Chung A, Lemp N, Chumakova K, Yin D, Wang HJ, Said J, Gui D, Miller CW (2008). "Functional domains of CCN1 (Cyr61) regulate breast cancer progression". Int. J. Oncol. 33 (1): 59–67. doi:10.3892/ijo.33.1.59. PMID 18575751.
  75. ^ D'Antonio KB, Toubaji A, Albadine R, Mondul AM, Platz EA, Netto GJ, Getzenberg RH (2010). "Extracellular matrix associated protein CYR61 is linked to prostate cancer development". J. Urol. 183 (4): 1604–1610. doi:10.1016/j.juro.2009.12.006. PMC 3349619. PMID 20172544.
  76. ^ Goodwin CR, Lal B, Zhou X, Ho S, Xia S, Taeger A, Murray J, Laterra J (2010). "Cyr61 mediates hepatocyte growth factor-dependent tumor cell growth, migration, and Akt activation". Cancer Res. 70 (7): 2932–2941. doi:10.1158/0008-5472.CAN-09-3570. PMC 2848876. PMID 20233866.
  77. ^ Lin MT, Zuon CY, Chang CC, Chen ST, Chen CP, Lin BR, Wang MY, Jeng YM, Chang KJ (2005). "Cyr61 induces gastric cancer cell motility/invasion via activation of the integrin/nuclear factor-κB/cyclooxygenase-2 signaling pathway". Clin. Cancer Res. 11 (16): 5809–5820. doi:10.1158/1078-0432.CCR-04-2639. PMID 16115920.
  78. ^ Chen CC, Lau LF (2010). "Deadly liaisons: fatal attraction between CCN matricellular proteins and the tumor necrosis factor family of cytokines". J. Cell Commun. Signal. 4 (1): 63–69. doi:10.1007/s12079-009-0080-4. PMC 2821476. PMID 19898959.
  79. ^ Schmitt CA (2003). "Senescence, apoptosis and therapy--cutting the lifelines of cancer". Nature Reviews Cancer. 3 (4): 286–295. doi:10.1038/nrc1044. PMID 12671667. S2CID 7107243.
  80. ^ Sakamoto S, Yokoyama M, Aoki M, Suzuki K, Kakehi Y, Saito Y (2004). "Induction and function of CYR61 (CCN1) in prostatic stromal and epithelial cells: CYR61 is required for prostatic cell proliferation". Prostate. 61 (4): 305–317. doi:10.1002/pros.20098. PMID 15389821. S2CID 21302082.
  81. ^ Tong X, Xie D, O'Kelly J, Miller CW, Muller-Tidow C, Koeffler HP (2001). "Cyr61, a member of CCN family, is a tumor suppressor in non-small cell lung cancer". J. Biol. Chem. 276 (50): 47709–47714. doi:10.1074/jbc.M107878200. PMID 11598125.
  82. ^ Chien W, Kumagai T, Miller CW, Desmond JC, Frank JM, Said JW, Koeffler HP (2004). "Cyr61 suppresses growth of human endometrial cancer cells". J. Biol. Chem. 279 (51): 53087–53096. doi:10.1074/jbc.M410254200. PMID 15471875.
  83. ^ Dobroff AS, Wang H, Melnikova VO, Villares GJ, Zigler M, Huang L, Bar-Eli M (2009). "Silencing cAMP-response element binding protein (CREB) identifies cysteine-rich protein 61 (CYR61) as a tumor suppressor gene in melanoma". J. Biol. Chem. 284 (38): 26194–26206. doi:10.1074/jbc.M109.019836. PMC 2758018. PMID 19632997.
Preuzeto iz "https://bs.wikipedia.org/w/index.php?title=CYR61&oldid=3380161"