Emerin interacts in vitro with the splicing-associated factor, YT521-B.
Emerin is a nuclear membrane protein that interacts with lamin A/C at the nuclear envelope. Mutations in either emerin or lamin A/C cause Emery-Dreifuss muscular dystrophy (EDMD). The functions of emerin are poorly understood, but EDMD affects mainly skeletal and cardiac muscle. We used a high-stringency yeast two-hybrid method to ... screen a human heart cDNA library, with full-length emerin as bait. Four out of five candidate interactors identified were nuclear proteins: lamin A, splicing factor YT521-B, proteasome subunit PA28 gamma and transcription factor vav-1. Specific binding between emerin and the functional C-terminal domain of YT521-B was confirmed by pull-down assays and biomolecular interaction analysis (BIAcore). Inhibition by emerin of YT521-B-dependent splice site selection in vivo suggests that the interaction is physiologically significant. A 'bipartite' binding site for YT521-B in emerin was identified using alanine substitution or disease-associated mutations in emerin. The transcription factor GCL (germ cell-less) has previously been shown to bind to the same site. The results are consistent with an emerging view that lamins and lamina-associated proteins, like emerin, have a regulatory role, as well as a structural role in the nucleus. YT521-B joins a growing list of candidates for a role in a gene expression model of the pathogenesis of EDMD.
Mesh Terms:
Binding Sites, Cell Nucleus, Cysteine Endopeptidases, DNA, Complementary, Drosophila Proteins, Gene Library, Genes, Reporter, Humans, Lamin Type A, Membrane Proteins, Multienzyme Complexes, Muscular Dystrophy, Emery-Dreifuss, Myocardium, Nerve Tissue Proteins, Nuclear Proteins, Open Reading Frames, Precipitin Tests, Proteasome Endopeptidase Complex, Protein Binding, Protein Structure, Tertiary, RNA, RNA Splicing, RNA, Messenger, RNA-Binding Proteins, Thymopoietins, Time Factors, Two-Hybrid System Techniques
Binding Sites, Cell Nucleus, Cysteine Endopeptidases, DNA, Complementary, Drosophila Proteins, Gene Library, Genes, Reporter, Humans, Lamin Type A, Membrane Proteins, Multienzyme Complexes, Muscular Dystrophy, Emery-Dreifuss, Myocardium, Nerve Tissue Proteins, Nuclear Proteins, Open Reading Frames, Precipitin Tests, Proteasome Endopeptidase Complex, Protein Binding, Protein Structure, Tertiary, RNA, RNA Splicing, RNA, Messenger, RNA-Binding Proteins, Thymopoietins, Time Factors, Two-Hybrid System Techniques
Eur. J. Biochem.
Date: Jun. 01, 2003
PubMed ID: 12755701
View in: Pubmed Google Scholar
Download Curated Data For This Publication
8728
Switch View:
- Interactions 9