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2017 | 77 | Suppl.1 |
Tytuł artykułu

Studies of CacyBP/SIP protein in beta-catenin dysregulation using m128 HD mice and the CacyBP zebrafish knockout

Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
INTRODUCTION: Mutated huntingtin has been shown to affect gene expression in brains of Huntington’s disease (HD) mice models. One of these genes is CacyBP/SIP encoding calcyclin-binding protein (CacyBP/SIP), which is 2-fold overexpressed in the striatum of YAC128 mice, a model of HD. A higher increase in the CacyBP/SIP dimer than in the monomer was found in the striatum of 3-month-old HD mice. Moreover, we detected a decrease in total protein ubiquitination, while the level of β‑catenin was higher in the striatum of HD transgenic mice as compared to wild-type mice. AIM(S): To determine the effect of increased dimerization of CacyBP/SIP protein in YAC128 model and the effect of decreased level of Cacybp in zebrafish on β‑catenin signaling. METHOD(S): Medium Spiny Neurons (MSNs) and glial cultures isolated from the striatum of YAC128 and wild‑type mice were used to analyze the level of β‑catenin and protein ubiquitination by western blotting. Proximity Ligation Assay (PLA) was used to study CacyBP/ SIP dimerization in these cultures. Zebrafish lines with knockout of cacybp were generated using CRISPR/Cas9 technology. RESULTS: We did not detect any changes in β‑catenin or total protein ubiquitination in MSN or glial cultures. We observed the presence of CacyBP/SIP dimers using PLA. Currently, we are studying if the increased level of CacyBP/SIP dimers affects β‑catenin and its ubiquitination in YAC128 MSNs. Preliminary data from the cacybp zebrafish knockout shows disturbances in β‑catenin protein level in total protein extracts. CONCLUSIONS: In MSNs and glial cells from YAC128 mice we did not find any changes in β‑catenin and protein ubiquitination, which were observed in the striatum of adult HD mice. Increased dimerization of CacyBP might disturb degradation of β‑catenin during aging in HD. The cacybp zebrafish knockouts will allow us to find out if Cacybp is involved in β‑catenin signaling and what are its other potential functions. FINANCIAL SUPPORT: This study was supported by The National Science Centre in Poland. Grant no. 2014/15/D/ NZ3/05181 for MCZ.
Słowa kluczowe
Wydawca
-
Rocznik
Tom
77
Numer
Opis fizyczny
p.67
Twórcy
autor
  • International Institute of Molecular and Cell Biology in Warsaw, Laboratory of Neurodegeneration, Warsaw, Poland
autor
  • International Institute of Molecular and Cell Biology in Warsaw, Laboratory of Neurodegeneration, Warsaw, Poland
  • Warsaw University of Life Sciences, Biotechnology, Warsaw, Poland
autor
  • International Institute of Molecular and Cell Biology in Warsaw, Laboratory of Neurodegeneration, Warsaw, Poland
Bibliografia
Typ dokumentu
Bibliografia
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Identyfikator YADDA
bwmeta1.element.agro-952a1400-226c-4a93-ab1b-e8a68699ee9f
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