About: Arf and Rho GAP adapter protein ARAP1 participates in the mobilization of TRAIL-R1/DR4 to the plasma membrane     Goto   Sponge   NotDistinct   Permalink

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  • TRAIL, a TNFa family ligand, induces apoptosis of cancer cells upon binding to receptors TRAIL-R1/DR4 and TRAIL-R2/DR5. This apoptosis is regulated at multiple levels; one is the presence and relative number of TRAIL pro- and anti-apoptotic receptors on cytoplasmic membrane. In a yeast two-hybrid search for proteins interacting with the intracellular part (ICP) of DR4 we picked ARAP1, an adapter protein with ArfGAP and RhoGAP activities. In yeast DR4(ICP) interacts with alternatively spliced ARAP1 lacking 11 aa from PH5 domain. Transfected ARAP1 co-precipitates with DR4 and co-localizes with it in the ER/Golgi, at the cytoplasmic membrane and in early endosomes of TRAIL-treated cells. ARAP1 knockdown significantly compromises localization of DR4 at the cell surface of several tumor cell lines and slows down their TRAIL-induced death. ARAP1 is thus likely involved in the regulation of cell-specific trafficking of DR4 and might affect the efficacy of TRAIL-induced apoptosis.
  • TRAIL, a TNFa family ligand, induces apoptosis of cancer cells upon binding to receptors TRAIL-R1/DR4 and TRAIL-R2/DR5. This apoptosis is regulated at multiple levels; one is the presence and relative number of TRAIL pro- and anti-apoptotic receptors on cytoplasmic membrane. In a yeast two-hybrid search for proteins interacting with the intracellular part (ICP) of DR4 we picked ARAP1, an adapter protein with ArfGAP and RhoGAP activities. In yeast DR4(ICP) interacts with alternatively spliced ARAP1 lacking 11 aa from PH5 domain. Transfected ARAP1 co-precipitates with DR4 and co-localizes with it in the ER/Golgi, at the cytoplasmic membrane and in early endosomes of TRAIL-treated cells. ARAP1 knockdown significantly compromises localization of DR4 at the cell surface of several tumor cell lines and slows down their TRAIL-induced death. ARAP1 is thus likely involved in the regulation of cell-specific trafficking of DR4 and might affect the efficacy of TRAIL-induced apoptosis. (en)
  • TRAIL, ligand z TNFa rodiny, indukuje svou vazbou na receptory smrti TRAIL-R1/DR4 a TRAIL-R2/DR5 apoptózu nádorových buněk. TRAILem indukovaná apoptóza je regulována na mnoha úrovních, jedna z nich je přítomnost a relativní množství TRAIL pro a anti-apoptotických receptorů na cytoplazmatické membráně. Kvasinkovým dvou-hybridním vyhledáváním proteinů interagujících s intracelulární část (ICP) DR4 jsme objevili ARAP1, adaptérový protein s ArfGAP a RhoGAP doménami. V kvasinkách interaguje DR4 (ICP) s alternativně sestřiženým ARAP1, kterému chybí 11 aminokyselin z PH5 domény. Transfekovaný ARAP1 koprecipituje s DR4 a kolokalizuje s ním v membránách ER /Golgi, cytoplazmy a také v raných endosomech. Potlačení exprese ARAP1 významně snižuje lokalizaci DR4 na povrchu některých nádorových buněk a zpomaluje TRAILem indukovanou apoptózu. Naše data ukazují, že ARAP1 se pravděpodobně podílí na regulaci buněčně-specifického transportu DR4 a může tak ovlivnit účinnost TRAILem indukované apoptózy. (cs)
Title
  • Arf and Rho GAP adapter protein ARAP1 participates in the mobilization of TRAIL-R1/DR4 to the plasma membrane
  • Arf and Rho GAP adapter protein ARAP1 participates in the mobilization of TRAIL-R1/DR4 to the plasma membrane (en)
  • Adaptérový protein ARAP1 s ARF a Rho GAP doménami se podílí na mobilizaci TRAIL-R1/DR4 na plasmatickou membránu (cs)
skos:prefLabel
  • Arf and Rho GAP adapter protein ARAP1 participates in the mobilization of TRAIL-R1/DR4 to the plasma membrane
  • Arf and Rho GAP adapter protein ARAP1 participates in the mobilization of TRAIL-R1/DR4 to the plasma membrane (en)
  • Adaptérový protein ARAP1 s ARF a Rho GAP doménami se podílí na mobilizaci TRAIL-R1/DR4 na plasmatickou membránu (cs)
skos:notation
  • RIV/68378050:_____/08:00315276!RIV09-AV0-68378050
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(1M0506), Z(AV0Z50520514)
http://linked.open...iv/cisloPeriodika
  • 3
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 357003
http://linked.open...ai/riv/idVysledku
  • RIV/68378050:_____/08:00315276
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • apoptosis; TRAIL; receptor trafficking (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [F33CAB2D211B]
http://linked.open...i/riv/nazevZdroje
  • Apoptosis
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 13
http://linked.open...iv/tvurceVysledku
  • Anděra, Ladislav
  • Klíma, Martin
  • Šourková, Vladimíra
  • Čermák, Lukáš
  • Šímová, Šárka
http://linked.open...ain/vavai/riv/wos
  • 000253574000010
http://linked.open...n/vavai/riv/zamer
issn
  • 1360-8185
number of pages
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