Fas ligand

Fas ligand (TNF superfamilija, član 6)
Identifikatori
Simboli	FASLG; APT1LG1; CD178; CD95L; FASL; TNFSF6
Vanjski ID	OMIM: 134638 MGI: 99255 HomoloGene: 533 GeneCards: FASLG Gene
Ontologija gena
Molekularna funkcija	• aktivnost prenosa signala; • citokinska aktivnost; • vezivanje za receptor faktora nekroze tumora;
Celularna komponenta	• ekstracelularni region; • ekstracelularni prostor; • integralno sa membranom plazme; • membrana;
Biološki proces	• apoptoza; • imunski odgovor; • transdukcija signala; • interćelijska signalizacija; • indukcija apoptoze putem ekstracelarnog signala; • pozitivna regulacija I-kappaB kinaze/NF-kappaB kaskada; • programirana ćelijska smrt retinalnih ćelija;
Pregled RNK izražavanja
	podaci
Ortolozi

edit

Fas ligand (FasL ili CD95L) je tip II transmembranski protein koji pripada TNF familiji. Njegovo vezivanje za FasR receptor indukuje apoptozu. Fas ligand/receptor interakcija igra važnu ulogu u regulaciji imunskog sistema i progresiji raka.^[1]

Struktura

Fas ligand je homotrimerni tip II transmembranski protein. On signalizira putem trimerizacije FasR, koji je lociran u membranama ciljnih ćelija. Ova trimerizacija obično dovodi do apoptoze, ili ćelijske smrti.

Rastvorni Fas ligand se generiše odvajanjem za membranu vezanog FasL na konzervisanom mestu odsecanja putem spoljašnje serin matriks metaloproteinaze MMP-7.

Receptori

FasR: Fas receptor, ili CD95, je najintenzivnije studirani član familije receptora ćelijske smrti. Gen ovog receptora je lociran na ljudskom hromozomu 10 i hromozomu 19 kod miševa. Do sada je identifikovano osam splajsovanih varijanti, koje su translirane u sedam izoformi proteina. Mnoge od tih izoformi su retki haplotipi koji su obično vezani za stanje bolesti. Fas receptor koji indukuje apoptozu se naziva izoforma 1 i on je tip 1 transmembranski protein. On se sastoji od tri cistein-bogata pseudo-ponavljanja, transmembranskog domena, i intracelularnog domena smrti.

DcR3: Mamac receptor 3 (DcR3) je nedavno otkriven receptor za superfamiliju Faktora nekroze tumora koji vezuje FasL, LIGHT, i TLA1. DcR3 je rastvoran receptor koji nema sposobnost prenosa signala (zato se naziva mamac). On funkcioniše tako što sprečava FasR-FasL interakciju putem kompetitivnog vezivanja za ligand koji je fiksiran na membrani, čime ga inaktivira.^[2]

Uloga u bolesti

Defektivna Fas posredovana apoptoza može da dovede do onkogeneze, kao i otpornosti postojećih tumora na lekove. Fas mutacije su bile vezane za autoimuni limfoproliferativni sindrom (ALPS).

Interakcije

Za Fas ligand je bilo pokazano da interaguje sa FADD,^[3]^[4] Grb2, ^[5]^[6] Kaspazom 8,^[3]^[4] Fas receptorom,^[3]^[4]^[7]^[8] FYN,^[6]^[9] EZR,^[3]^[10] PACSIN2,^[5] FNBP1^[5] i TNFRSF6B.^[11]^[12]^[13]

Reference

↑ Mire-Sluis, Anthony R.; Thorpe, Robin, ur. (1998). Cytokines (Handbook of Immunopharmacology). Boston: Academic Press. ISBN 0-12-498340-5.
↑ Sheikh MS, Fornace AJ (2000). „Death and decoy receptors and p53-mediated apoptosis”. Leukemia 14 (8): 1509–13. DOI:10.1038/sj.leu.2401865. PMID 10942251.
↑ ^3,0 ^3,1 ^3,2 ^3,3 Gajate, Consuelo; Mollinedo Faustino (March 2005). „Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy”. J. Biol. Chem. (United States) 280 (12): 11641–7. DOI:10.1074/jbc.M411781200. ISSN 0021-9258. PMID 15659383.
↑ ^4,0 ^4,1 ^4,2 Micheau, Olivier; Tschopp Jürg (2003). „Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes”. Cell (United States) 114 (2): 181–90. DOI:10.1016/S0092-8674(03)00521-X. ISSN 0092-8674. PMID 12887920.
↑ ^5,0 ^5,1 ^5,2 Ghadimi, Markus Philipp; Sanzenbacher Ralf, Thiede Bernd, Wenzel Jennifer, Jing Qian, Plomann Markus, Borkhardt Arndt, Kabelitz Dieter, Janssen Ottmar (May 2002). „Identification of interaction partners of the cytosolic polyproline region of CD95 ligand (CD178)”. FEBS Lett. (Netherlands) 519 (1-3): 50–8. DOI:10.1016/S0014-5793(02)02709-6. ISSN 0014-5793. PMID 12023017.
↑ ^6,0 ^6,1 Wenzel, J; Sanzenbacher R, Ghadimi M, Lewitzky M, Zhou Q, Kaplan D R, Kabelitz D, Feller S M, Janssen O (Dec 2001). „Multiple interactions of the cytosolic polyproline region of the CD95 ligand: hints for the reverse signal transduction capacity of a death factor”. FEBS Lett. (Netherlands) 509 (2): 255–62. DOI:10.1016/S0014-5793(01)03174-X. ISSN 0014-5793. PMID 11741599.
↑ Starling, G C; Bajorath J, Emswiler J, Ledbetter J A, Aruffo A, Kiener P A (April 1997). „Identification of amino acid residues important for ligand binding to Fas”. J. Exp. Med. (UNITED STATES) 185 (8): 1487–92. DOI:10.1084/jem.185.8.1487. ISSN 0022-1007. PMC 2196280. PMID 9126929.
↑ Schneider, P; Bodmer J L, Holler N, Mattmann C, Scuderi P, Terskikh A, Peitsch M C, Tschopp J (July 1997). „Characterization of Fas (Apo-1, CD95)-Fas ligand interaction”. J. Biol. Chem. (UNITED STATES) 272 (30): 18827–33. DOI:10.1074/jbc.272.30.18827. ISSN 0021-9258. PMID 9228058.
↑ Hane, M; Lowin B, Peitsch M, Becker K, Tschopp J (October 1995). „Interaction of peptides derived from the Fas ligand with the Fyn-SH3 domain”. FEBS Lett. (NETHERLANDS) 373 (3): 265–8. DOI:10.1016/0014-5793(95)01051-F. ISSN 0014-5793. PMID 7589480.
↑ Parlato, S; Giammarioli A M, Logozzi M, Lozupone F, Matarrese P, Luciani F, Falchi M, Malorni W, Fais S (October 2000). „CD95 (APO-1/Fas) linkage to the actin cytoskeleton through ezrin in human T lymphocytes: a novel regulatory mechanism of the CD95 apoptotic pathway”. EMBO J. (ENGLAND) 19 (19): 5123–34. DOI:10.1093/emboj/19.19.5123. ISSN 0261-4189. PMC 302100. PMID 11013215.
↑ Yu, K Y; Kwon B, Ni J, Zhai Y, Ebner R, Kwon B S (May 1999). „A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis”. J. Biol. Chem. (UNITED STATES) 274 (20): 13733–6. DOI:10.1074/jbc.274.20.13733. ISSN 0021-9258. PMID 10318773.
↑ Hsu, Tsui-Ling; Chang Yung-Chi, Chen Siu-Ju, Liu Yong-Jun, Chiu Allen W, Chio Chung-Ching, Chen Lieping, Hsieh Shie-Liang (May 2002). „Modulation of dendritic cell differentiation and maturation by decoy receptor 3”. J. Immunol. (United States) 168 (10): 4846–53. ISSN 0022-1767. PMID 11994433.
↑ Pitti, R M; Marsters S A, Lawrence D A, Roy M, Kischkel F C, Dowd P, Huang A, Donahue C J, Sherwood S W, Baldwin D T, Godowski P J, Wood W I, Gurney A L, Hillan K J, Cohen R L, Goddard A D, Botstein D, Ashkenazi A (December 1998). „Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer”. Nature (ENGLAND) 396 (6712): 699–703. DOI:10.1038/25387. ISSN 0028-0836. PMID 9872321.

Literatura

Choi C, Benveniste EN (2004). „Fas ligand/Fas system in the brain: regulator of immune and apoptotic responses.”. Brain Res. Brain Res. Rev. 44 (1): 65–81. DOI:10.1016/j.brainresrev.2003.08.007. PMID 14739003.
Tolstrup M, Ostergaard L, Laursen AL, et al. (2004). „HIV/SIV escape from immune surveillance: focus on Nef.”. Curr. HIV Res. 2 (2): 141–51. DOI:10.2174/1570162043484924. PMID 15078178.

Vanjske veze

Online Mendelovsko nasleđivanje kod čoveka (OMIM) 601859
MeSH Fas+Ligand+Protein

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

[pmid10942251-2] Sheikh MS, Fornace AJ (2000). „Death and decoy receptors and p53-mediated apoptosis”. Leukemia 14 (8): 1509–13. DOI:10.1038/sj.leu.2401865. PMID 10942251.

[pmid15659383-3] 3,0 ^3,1 ^3,2 ^3,3 Gajate, Consuelo; Mollinedo Faustino (March 2005). „Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy”. J. Biol. Chem. (United States) 280 (12): 11641–7. DOI:10.1074/jbc.M411781200. ISSN 0021-9258. PMID 15659383.

[pmid12887920-4] 4,0 ^4,1 ^4,2 Micheau, Olivier; Tschopp Jürg (2003). „Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes”. Cell (United States) 114 (2): 181–90. DOI:10.1016/S0092-8674(03)00521-X. ISSN 0092-8674. PMID 12887920.

[pmid12023017-5] 5,0 ^5,1 ^5,2 Ghadimi, Markus Philipp; Sanzenbacher Ralf, Thiede Bernd, Wenzel Jennifer, Jing Qian, Plomann Markus, Borkhardt Arndt, Kabelitz Dieter, Janssen Ottmar (May 2002). „Identification of interaction partners of the cytosolic polyproline region of CD95 ligand (CD178)”. FEBS Lett. (Netherlands) 519 (1-3): 50–8. DOI:10.1016/S0014-5793(02)02709-6. ISSN 0014-5793. PMID 12023017.

[pmid11741599-6] 6,0 ^6,1 Wenzel, J; Sanzenbacher R, Ghadimi M, Lewitzky M, Zhou Q, Kaplan D R, Kabelitz D, Feller S M, Janssen O (Dec 2001). „Multiple interactions of the cytosolic polyproline region of the CD95 ligand: hints for the reverse signal transduction capacity of a death factor”. FEBS Lett. (Netherlands) 509 (2): 255–62. DOI:10.1016/S0014-5793(01)03174-X. ISSN 0014-5793. PMID 11741599.

[pmid9126929-7] Starling, G C; Bajorath J, Emswiler J, Ledbetter J A, Aruffo A, Kiener P A (April 1997). „Identification of amino acid residues important for ligand binding to Fas”. J. Exp. Med. (UNITED STATES) 185 (8): 1487–92. DOI:10.1084/jem.185.8.1487. ISSN 0022-1007. PMC 2196280. PMID 9126929.

[pmid9228058-8] Schneider, P; Bodmer J L, Holler N, Mattmann C, Scuderi P, Terskikh A, Peitsch M C, Tschopp J (July 1997). „Characterization of Fas (Apo-1, CD95)-Fas ligand interaction”. J. Biol. Chem. (UNITED STATES) 272 (30): 18827–33. DOI:10.1074/jbc.272.30.18827. ISSN 0021-9258. PMID 9228058.

[pmid7589480-9] Hane, M; Lowin B, Peitsch M, Becker K, Tschopp J (October 1995). „Interaction of peptides derived from the Fas ligand with the Fyn-SH3 domain”. FEBS Lett. (NETHERLANDS) 373 (3): 265–8. DOI:10.1016/0014-5793(95)01051-F. ISSN 0014-5793. PMID 7589480.

[pmid11013215-10] Parlato, S; Giammarioli A M, Logozzi M, Lozupone F, Matarrese P, Luciani F, Falchi M, Malorni W, Fais S (October 2000). „CD95 (APO-1/Fas) linkage to the actin cytoskeleton through ezrin in human T lymphocytes: a novel regulatory mechanism of the CD95 apoptotic pathway”. EMBO J. (ENGLAND) 19 (19): 5123–34. DOI:10.1093/emboj/19.19.5123. ISSN 0261-4189. PMC 302100. PMID 11013215.

[pmid10318773-11] Yu, K Y; Kwon B, Ni J, Zhai Y, Ebner R, Kwon B S (May 1999). „A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis”. J. Biol. Chem. (UNITED STATES) 274 (20): 13733–6. DOI:10.1074/jbc.274.20.13733. ISSN 0021-9258. PMID 10318773.

[pmid11994433-12] Hsu, Tsui-Ling; Chang Yung-Chi, Chen Siu-Ju, Liu Yong-Jun, Chiu Allen W, Chio Chung-Ching, Chen Lieping, Hsieh Shie-Liang (May 2002). „Modulation of dendritic cell differentiation and maturation by decoy receptor 3”. J. Immunol. (United States) 168 (10): 4846–53. ISSN 0022-1767. PMID 11994433.

[pmid9872321-13] Pitti, R M; Marsters S A, Lawrence D A, Roy M, Kischkel F C, Dowd P, Huang A, Donahue C J, Sherwood S W, Baldwin D T, Godowski P J, Wood W I, Gurney A L, Hillan K J, Cohen R L, Goddard A D, Botstein D, Ashkenazi A (December 1998). „Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer”. Nature (ENGLAND) 396 (6712): 699–703. DOI:10.1038/25387. ISSN 0028-0836. PMID 9872321.

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