CXCL12

Hemokin (C-X-C motif) ligand 12; (stromalne ćelije - izvedeni faktor 1)
	; PDB prikaz baziran na 1a15.
Dostupne strukture
	1a15, 1qg7, 1sdf, 1vmc, 2j7z, 2nwg, 2sdf
Identifikatori
Simboli	CXCL12; PBSF; SCYB12; SDF-1a; SDF-1b; SDF1; SDF1A; SDF1B; TLSF-a; TLSF-b; TPAR1
Vanjski ID	OMIM: 600835 MGI: 103556 HomoloGene: 507 GeneCards: CXCL12 Gene
Ontologija gena
Molekularna funkcija	• transdukcija signala; • hemokinska aktivnost; • aktivnost faktora rasta;
Celularna komponenta	• ekstracelularni region; • ekstracelularni prostor;
Biološki proces	• ćelijska homeostaza kalcijum jona; • hemotaksa; • inflamatorni odgovor; • imunski odgovor; • ćelijska adhezija; • transdukcija signala; • G-protein spregnuti receptor proteinski signalni put; • interćelijska signalizacija; • cirkulacija; • regulacija aktin polimerizacije i/ili depolimerizacije; • respons na viruse;
Pregled RNK izražavanja
	podaci
Ortolozi

edit

CXCL12, ili SDF-1 (stromalne ćelije-izvedeni faktor-1), je mali citokin iz hemokin familije. Ovaj molekul je zvanično zove hemokin (C-X-C motiv) ligand 12.^[1]

SDF-1 alfa i beta su mali citokini iz interkrin familije čiji članovi aktiviraju leukocite i često indukuju proinflamatorne stimuluse kao što su lipopolisaharid, TNF, ili IL1. Interkrini su karakterizovani prisustvom 4 konzervirana cisteina koji formiraju dva disulfidna mosta. The SDF1 proteini pripadaju CXC grupi citokina.^[2]

Struktura uredi

SDF-1 proizvodi u dve forme, SDF-1α/CXCL12a i SDF-1β/CXCL12b, putem alternativnog splajsovanja gena.^[3]

Funkcija uredi

Hemotaksa uredi

CXCL12 izaziva potentnu hemotaksu limfocita.^[4]^[5]^[6]^[7] Tokom embriogeneze on usmerava migraciju hematopoetskih ćelija i formiranje velikih krvnih sudova. Miševi bez CXCL12 gena su letalni pre rođenja, ili u toku prvog sata života.

Kod odraslih CXCL12 igra važnu ulogu u angiogenezi putem regrutovanja endotelnih progenitorskih ćelija (EPC) iz koštane srži kroz CXCR4 zavistan mehanizam.^[8] Ova funkcija čini CXCL12 veoma važnim faktorom u karcinogenezi i neovaskularizaciji vezanoj za progresiju tumora.^[9] CXCL12 takođe ima ulogu u metastazi tumora gde su ćelije raka koje izražavaju CXCR4 receptor privučene ka metastaznim ciljnim tkivima koja oslobađaju ligand, CXCL12.^[10] Kod raka dojke, međutim, povećano CXCL12 izražavanje određuje umanjeni rizik od metastaze.^[11]^[12]

Drugo uredi

Za CXCL12 je bilo pokazano da je izražen u mnogim tkivima kod miševa (uključujući mozak, timus, srce, pluća, jetru, bubrege, slezinu i kičmenu moždinu).

Receptor uredi

Receptor za ovaj hemokin je CXCR4, koji je ranije bio nazivan fuzin.^[13] CXCL12-CXCR4 interakcija je nekad bila smatrana eksluzivnom (za razliku od drugih hemokina i njihovih receptora), ali je nedavno bilo predloženo da se CXCL12 možda takođe vezuje za CXCR7 receptor.^[14]^[15]

Gen uredi

Gene za CXCL12 je lociran na ljudskom hromozomu 10.^[16]^[17] Kod ljudi i miševa CXCL12 i CXCR4 imaju visok identitet sekvence: 99% i 90%, respektivno.

Reference uredi

↑ Mire-Sluis, Anthony R.; Thorpe, Robin, ur. (1998). Cytokines (Handbook of Immunopharmacology). Boston: Academic Press. ISBN 0-12-498340-5.
↑ „Entrez Gene: CXCL12 chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)”.
↑ De La Luz Sierra M, Yang F, Narazaki M, Salvucci O, Davis D, Yarchoan R, Zhang HH, Fales H, Tosato G (April 2004). „Differential processing of stromal-derived factor-1alpha and stromal-derived factor-1beta explains functional diversity”. Blood 103 (7): 2452–9. DOI:10.1182/blood-2003-08-2857. PMID 14525775.
↑ Bleul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A, Springer TA (September 1996). „A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1)”. J. Exp. Med. 184 (3): 1101–9. PMC 2192798. PMID 9064327.
↑ Ara T, Nakamura Y, Egawa T, Sugiyama T, Abe K, Kishimoto T, Matsui Y, Nagasawa T (April 2003). „Impaired colonization of the gonads by primordial germ cells in mice lacking a chemokine, stromal cell-derived factor-1 (SDF-1)”. Proc. Natl. Acad. Sci. U.S.A. 100 (9): 5319–23. DOI:10.1073/pnas.0730719100. PMC 154343. PMID 12684531.
↑ Askari AT, Unzek S, Popovic ZB, Goldman CK, Forudi F, Kiedrowski M, Rovner A, Ellis SG, Thomas JD, DiCorleto PE, Topol EJ, Penn MS (August 2003). „Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy”. Lancet 362 (9385): 697–703. DOI:10.1016/S0140-6736(03)14232-8. PMID 12957092.
↑ Ma Q, Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, Bronson RT, Springer TA (August 1998). „Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice”. Proc. Natl. Acad. Sci. U.S.A. 95 (16): 9448–53. PMC 21358. PMID 9689100.
↑ Zheng H, Fu G, Dai T, Huang H (September 2007). „Migration of endothelial progenitor cells mediated by stromal cell-derived factor-1alpha/CXCR4 via PI3K/Akt/eNOS signal transduction pathway”. J. Cardiovasc. Pharmacol. 50 (3): 274–80. DOI:10.1097/FJC.0b013e318093ec8f. PMID 17878755.
↑ Kryczek I, Wei S, Keller E, Liu R, Zou W (March 2007). „Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis”. Am. J. Physiol., Cell Physiol. 292 (3): C987–95. DOI:10.1152/ajpcell.00406.2006. PMID 16943240.
↑ Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verástegui E, Zlotnik A (March 2001). „Involvement of chemokine receptors in breast cancer metastasis”. Nature 410 (6824): 50–6. DOI:10.1038/35065016. PMID 11242036.
↑ Mirisola V, Zuccarino A, Bachmeier BE, Sormani MP, Falter J, Nerlich A, Pfeffer U (September 2009). „CXCL12/SDF1 expression by breast cancers is an independent prognostic marker of disease-free and overall survival”. Eur. J. Cancer 45 (14): 2579–87. DOI:10.1016/j.ejca.2009.06.026. PMID 19646861.
↑ Wendt MK, Cooper AN, Dwinell MB (February 2008). „Epigenetic silencing of CXCL12 increases the metastatic potential of mammary carcinoma cells”. Oncogene 27 (10): 1461–71. DOI:10.1038/sj.onc.1210751. PMID 17724466.
↑ Bleul et al. (1996). „The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry”. Nature 382: 829-833.
↑ Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, Arenzana-Seisdedos F, Thelen M, Bachelerie F (October 2005). „The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes”. J. Biol. Chem. 280 (42): 35760–6. DOI:10.1074/jbc.M508234200. PMID 16107333.
↑ Burns JM, Summers BC, Wang Y, Melikian A, Berahovich R, Miao Z, Penfold ME, Sunshine MJ, Littman DR, Kuo CJ, Wei K, McMaster BE, Wright K, Howard MC, Schall TJ (September 2006). „A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development”. J. Exp. Med. 203 (9): 2201–13. DOI:10.1084/jem.20052144. PMC 2118398. PMID 16940167.
↑ Shirozu M, Nakano T, Inazawa J, et al. (August 1995). „Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene”. Genomics 28 (3): 495–500. DOI:10.1006/geno.1995.1180. PMID 7490086.
↑ Deloukas P, Earthrowl ME, Grafham DV, et al. (May 2004). „The DNA sequence and comparative analysis of human chromosome 10”. Nature 429 (6990): 375–81. DOI:10.1038/nature02462. PMID 15164054.

Literatura uredi

Kucia M, Reca R, Miekus K, et al. (2005). „Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis”. Stem Cells 23 (7): 879–94. DOI:10.1634/stemcells.2004-0342. PMID 15888687.
Kryczek I, Wei S, Keller E, et al. (2007). „Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis”. Am. J. Physiol., Cell Physiol. 292 (3): C987–95. DOI:10.1152/ajpcell.00406.2006. PMID 16943240.
Stellos K, Gawaz M (2007). „Platelets and stromal cell-derived factor-1 in progenitor cell recruitment”. Semin. Thromb. Hemost. 33 (2): 159–64. DOI:10.1055/s-2007-969029. PMID 17340464.
Arya M, Ahmed H, Silhi N, et al. (2007). „Clinical importance and therapeutic implications of the pivotal CXCL12-CXCR4 (chemokine ligand-receptor) interaction in cancer cell migration”. Tumour Biol. 28 (3): 123–31. DOI:10.1159/000102979. PMID 17510563.

[1] Mire-Sluis, Anthony R.; Thorpe, Robin, ur. (1998). Cytokines (Handbook of Immunopharmacology). Boston: Academic Press. ISBN 0-12-498340-5.

[2] „Entrez Gene: CXCL12 chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)”.

[pmid14525775-3] De La Luz Sierra M, Yang F, Narazaki M, Salvucci O, Davis D, Yarchoan R, Zhang HH, Fales H, Tosato G (April 2004). „Differential processing of stromal-derived factor-1alpha and stromal-derived factor-1beta explains functional diversity”. Blood 103 (7): 2452–9. DOI:10.1182/blood-2003-08-2857. PMID 14525775.

[pmid9064327-4] Bleul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A, Springer TA (September 1996). „A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1)”. J. Exp. Med. 184 (3): 1101–9. PMC 2192798. PMID 9064327.

[pmid12684531-5] Ara T, Nakamura Y, Egawa T, Sugiyama T, Abe K, Kishimoto T, Matsui Y, Nagasawa T (April 2003). „Impaired colonization of the gonads by primordial germ cells in mice lacking a chemokine, stromal cell-derived factor-1 (SDF-1)”. Proc. Natl. Acad. Sci. U.S.A. 100 (9): 5319–23. DOI:10.1073/pnas.0730719100. PMC 154343. PMID 12684531.

[pmid12957092-6] Askari AT, Unzek S, Popovic ZB, Goldman CK, Forudi F, Kiedrowski M, Rovner A, Ellis SG, Thomas JD, DiCorleto PE, Topol EJ, Penn MS (August 2003). „Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy”. Lancet 362 (9385): 697–703. DOI:10.1016/S0140-6736(03)14232-8. PMID 12957092.

[pmid9689100-7] Ma Q, Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, Bronson RT, Springer TA (August 1998). „Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice”. Proc. Natl. Acad. Sci. U.S.A. 95 (16): 9448–53. PMC 21358. PMID 9689100.

[pmid17878755-8] Zheng H, Fu G, Dai T, Huang H (September 2007). „Migration of endothelial progenitor cells mediated by stromal cell-derived factor-1alpha/CXCR4 via PI3K/Akt/eNOS signal transduction pathway”. J. Cardiovasc. Pharmacol. 50 (3): 274–80. DOI:10.1097/FJC.0b013e318093ec8f. PMID 17878755.

[pmid16943240-9] Kryczek I, Wei S, Keller E, Liu R, Zou W (March 2007). „Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis”. Am. J. Physiol., Cell Physiol. 292 (3): C987–95. DOI:10.1152/ajpcell.00406.2006. PMID 16943240.

[pmid11242036-10] Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verástegui E, Zlotnik A (March 2001). „Involvement of chemokine receptors in breast cancer metastasis”. Nature 410 (6824): 50–6. DOI:10.1038/35065016. PMID 11242036.

[pmid19646861-11] Mirisola V, Zuccarino A, Bachmeier BE, Sormani MP, Falter J, Nerlich A, Pfeffer U (September 2009). „CXCL12/SDF1 expression by breast cancers is an independent prognostic marker of disease-free and overall survival”. Eur. J. Cancer 45 (14): 2579–87. DOI:10.1016/j.ejca.2009.06.026. PMID 19646861.

[pmid17724466-12] Wendt MK, Cooper AN, Dwinell MB (February 2008). „Epigenetic silencing of CXCL12 increases the metastatic potential of mammary carcinoma cells”. Oncogene 27 (10): 1461–71. DOI:10.1038/sj.onc.1210751. PMID 17724466.

[13] Bleul et al. (1996). „The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry”. Nature 382: 829-833.

[pmid16107333-14] Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, Arenzana-Seisdedos F, Thelen M, Bachelerie F (October 2005). „The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes”. J. Biol. Chem. 280 (42): 35760–6. DOI:10.1074/jbc.M508234200. PMID 16107333.

[pmid16940167-15] Burns JM, Summers BC, Wang Y, Melikian A, Berahovich R, Miao Z, Penfold ME, Sunshine MJ, Littman DR, Kuo CJ, Wei K, McMaster BE, Wright K, Howard MC, Schall TJ (September 2006). „A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development”. J. Exp. Med. 203 (9): 2201–13. DOI:10.1084/jem.20052144. PMC 2118398. PMID 16940167.

[pmid7490086-16] Shirozu M, Nakano T, Inazawa J, et al. (August 1995). „Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene”. Genomics 28 (3): 495–500. DOI:10.1006/geno.1995.1180. PMID 7490086.

[pmid15164054-17] Deloukas P, Earthrowl ME, Grafham DV, et al. (May 2004). „The DNA sequence and comparative analysis of human chromosome 10”. Nature 429 (6990): 375–81. DOI:10.1038/nature02462. PMID 15164054.

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