Publication
Title
Mutations in ADNP affect expression and subcellular localization of the protein
Author
Abstract
Truncating de novo mutations in ADNP have been identified in patients with the Helsmoortel-Van der Aa syndrome. However correlations between the distinct mutations and their impact on the protein have not been studied before. Here we report the effect of mutations in ADNP by examining the expression and subcellular localization of GFP-tagged mutant transcripts in transfected HEK293T cells. ADNP encloses a bipartite nuclear localization signal and we found mutations therein to stall the mutant protein within the cytoplasm. Using immunocytochemistry, we could demonstrate colocalization of wild-type ADNP with heterochromatin. We found mutations presenting a pattern based on the genetic position. For certain mutant proteins enrichment at pericentromeric heterochromatin seems partially lost. Finally, N-terminal truncated ADNP mutants are routed towards cytosolic proteasomal degradation and rescued with the proteasome inhibitor MG132. Our results suggest a correlation between the position of the mutations across the protein, its stability and subcellular localization.
Language
English
Source (journal)
Cell cycle. - Place of publication unknown
Publication
Place of publication unknown : 2018
ISSN
1538-4101
Volume/pages
17 :9 (2018) , p. 1068-1075
ISI
000442407800005
Pubmed ID
29911927
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 08.10.2018
Last edited 20.09.2021
To cite this reference