Abstract
Scaffold attachment factor B1 (SAFB1) is an integral component of the nuclear matrix of vertebrate cells. It binds to DNA on scaffold/matrix attachment region elements, as well as to RNA and a multitude of different proteins, affecting basic cellular activities such as transcription, splicing and DNA damage repair. In the present study, we show that enhancer of rudimentary homologue (ERH) is a new molecular partner of SAFB1 and its 70% homologous paralogue, scaffold attachment factor B2 (SAFB2). ERH interacts directly in the nucleus with the C-terminal Arg-Gly-rich region of SAFB1/2 and co-localizes with it in the insoluble nuclear fraction. ERH, a small ubiquitous protein with striking homology among species and a unique structure, has also been implicated in fundamental cellular mechanisms. Our functional analyses suggest that the SAFB/ERH interaction does not affect SAFB1/2 function in transcription (e.g. as oestrogen receptor α co-repressors), although it reverses the inhibition exerted by SAFB1/2 on the splicing kinase SR protein kinase 1 (SRPK1), which also binds on the C-terminus of SAFB1/2. Accordingly, ERH silencing decreases lamin B receptor and SR protein phosphorylation, which are major SRPK1 substrates, further substantiating the role of SAFB1 and SAFB2 in the co-ordination of nuclear function.
Keywords:
ERH; SAFB; SR protein; SRPK1; nuclear matrix.
© 2017 Federation of European Biochemical Societies.
MeSH terms
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Active Transport, Cell Nucleus
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Animals
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Cell Cycle Proteins / antagonists & inhibitors
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Cell Cycle Proteins / chemistry
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Line, Tumor
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Genes, Reporter
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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HEK293 Cells
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Humans
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Matrix Attachment Region Binding Proteins / chemistry
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Matrix Attachment Region Binding Proteins / genetics
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Matrix Attachment Region Binding Proteins / metabolism*
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Microscopy, Fluorescence
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Nuclear Matrix-Associated Proteins / chemistry
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Nuclear Matrix-Associated Proteins / genetics
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Nuclear Matrix-Associated Proteins / metabolism*
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Peptide Fragments / chemistry
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Phosphorylation
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Protein Interaction Domains and Motifs
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Protein Multimerization
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Protein Processing, Post-Translational*
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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RNA Interference
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Rats
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Receptors, Estrogen / chemistry
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Receptors, Estrogen / genetics
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Receptors, Estrogen / metabolism*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Serine-Arginine Splicing Factors / chemistry
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Serine-Arginine Splicing Factors / metabolism*
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Two-Hybrid System Techniques
Substances
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Cell Cycle Proteins
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ERH protein, human
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Matrix Attachment Region Binding Proteins
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Nuclear Matrix-Associated Proteins
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Peptide Fragments
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Receptors, Estrogen
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Recombinant Fusion Proteins
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SAFB protein, human
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SAFB2 protein, human
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Transcription Factors
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Green Fluorescent Proteins
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Serine-Arginine Splicing Factors
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SRPK1 protein, human
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Protein Serine-Threonine Kinases