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Mislocalization of human transcription factor MOK2 in the presence of pathogenic mutations of lamin A/C
Author(s) -
Dreuillet Caroline,
Harper Maryannick,
Tillit Jeanne,
Kress Michel,
ErnoultLange Michèle
Publication year - 2008
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1042/bc20070053
Subject(s) - lamin , biology , nuclear lamina , transcription factor , repressor , dna binding protein , genetics , nuclear protein , activator (genetics) , mutant , gene , microbiology and biotechnology , transcription (linguistics) , philosophy , linguistics
Background information . hsMOK2 (human MOK2) is a DNA‐binding transcriptional repressor. For example, it represses the IRBP (interphotoreceptor retinoid‐binding protein) gene by competing with the CRX (cone‐rod homeobox protein) transcriptional activator for DNA binding. Previous studies have shown an interaction between hsMOK2 and nuclear lamin A/C. This interaction could be important to explain hsMOK2 ability to repress transcription. Results . In the present study, we have tested whether missense pathogenic mutations of lamin A/C, which are located in the hsMOK2‐binding domain, could affect the interaction with hsMOK2. We find that none of the tested mutations is able to disrupt hsMOK2 binding in vitro or in vivo . However, we observe an aberrant cellular localization of hsMOK2 into nuclear aggregates when pathogenic lamin A/C mutant proteins are expressed. Conclusions . These results indicate that pathogenic mutations in lamin A/C lead to sequestration of hsMOK2 into nuclear aggregates, which may deregulate MOK2 target genes.