About: Structural and Functional Characterization of the Wnt Inhibitor APC Membrane Recruitment 1 (Amer1)     Goto   Sponge   NotDistinct   Permalink

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  • Amer1/WTX binds to the tumor suppressor adenomatous polyposis coli and acts as an inhibitor of Wnt signaling by inducing beta catenin degradation. We show here that Amer1 directly interacts with the armadillo repeats of beta catenin via a domain consisting of repeated arginine-glutamic acid-alanine (REA) motifs, and that Amer1 assembles the beta catenin destruction complex at the plasma membrane by recruiting beta catenin, adenomatous polyposis coli, and Axin/Conductin. Deletion or specific mutations of the membrane binding domain of Amer1 abolish its membrane localization and abrogate negative control of Wnt signaling, which can be restored by artificial targeting of Amer1 to the plasma membrane. In line, a natural splice variant of Amer1 lacking the plasma membrane localization domain is deficient for Wnt inhibition. Knockdown of Amer1 leads to the activation of Wnt target genes, preferentially in dense compared with sparse cell cultures, suggesting that Amer1 function is regulated by cell contacts.
  • Amer1/WTX binds to the tumor suppressor adenomatous polyposis coli and acts as an inhibitor of Wnt signaling by inducing beta catenin degradation. We show here that Amer1 directly interacts with the armadillo repeats of beta catenin via a domain consisting of repeated arginine-glutamic acid-alanine (REA) motifs, and that Amer1 assembles the beta catenin destruction complex at the plasma membrane by recruiting beta catenin, adenomatous polyposis coli, and Axin/Conductin. Deletion or specific mutations of the membrane binding domain of Amer1 abolish its membrane localization and abrogate negative control of Wnt signaling, which can be restored by artificial targeting of Amer1 to the plasma membrane. In line, a natural splice variant of Amer1 lacking the plasma membrane localization domain is deficient for Wnt inhibition. Knockdown of Amer1 leads to the activation of Wnt target genes, preferentially in dense compared with sparse cell cultures, suggesting that Amer1 function is regulated by cell contacts. (en)
Title
  • Structural and Functional Characterization of the Wnt Inhibitor APC Membrane Recruitment 1 (Amer1)
  • Structural and Functional Characterization of the Wnt Inhibitor APC Membrane Recruitment 1 (Amer1) (en)
skos:prefLabel
  • Structural and Functional Characterization of the Wnt Inhibitor APC Membrane Recruitment 1 (Amer1)
  • Structural and Functional Characterization of the Wnt Inhibitor APC Membrane Recruitment 1 (Amer1) (en)
skos:notation
  • RIV/00216224:14310/11:00054246!RIV12-MSM-14310___
http://linked.open...avai/riv/aktivita
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  • S, Z(MSM0021622430)
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  • 22
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  • 232722
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  • RIV/00216224:14310/11:00054246
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  • Amer1 wtx REA motifs beta catenin wnt signaling Axin (en)
http://linked.open.../riv/klicoveSlovo
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  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [E97F125C654A]
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  • JOURNAL OF BIOLOGICAL CHEMISTRY
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  • 286
http://linked.open...iv/tvurceVysledku
  • Behrens, J.
  • Bryja, Vítězslav
  • Kříž, Vítězslav
  • Tanneberger, K.
  • Pfister, A.
  • Schambony, A.
http://linked.open...ain/vavai/riv/wos
  • 000291027700003
http://linked.open...n/vavai/riv/zamer
issn
  • 0021-9258
number of pages
http://bibframe.org/vocab/doi
  • 10.1074/jbc.M111.224881
http://localhost/t...ganizacniJednotka
  • 14310
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