title: Nuclear interaction of the dynein light chain LC8a with the TRPS1 transcription factor suppresses the transcriptional repression activity of TRPS1.
abstract: The TRPS1 gene codes for a 1281 amino acids nuclear transcription factor with an unusual combination of different types of zinc finger motifs, including GATA-type DNA-binding and IKAROS-like zinc fingers. TRPS1 is a repressor of GATA-regulated genes and implicated in the human tricho-rhino-phalangeal syndromes. We found that two distinct regions of TRPS1 can physically interact with the dynein light chain 8 protein, LC8a, that are at least 458 amino acids apart from each other. Region A covers 89 amino acids (635-723), spanning three potential C(2)H(2) zinc finger structures, and region B covers the 100 most C-terminal amino acids (1182-1281) containing the IKAROS-like motif. LC8a is known to interact with more than 10 different molecules, both proteins and nucleic acids. In most cases, LC8a was identified as a transport molecule in the cytoplasm. Interestingly, we found that LC8a co-localizes with TRPS1 in dot-like structures in the cell nucleus. In an electrophoretic mobility shift assay we could show that the interaction of LC8a and TRPS1 lowers the binding of TRPS1 to the GATA consensus sequence. In addition, GATA-regulated reporter gene assay indicated that LC8a is able to suppress the transcriptional repression activity of TRPS1.
authors.affiliation: Institut für Humangenetik, Universitätsklinikum, Hufelandstr. 55, D-45122 Essen, Germany.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Kaiser
authors.forename: Kamiab
authors.initials: K
authors.lastname: Tavassoli
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: Van den Bemd
authors.forename: Glenn T G
authors.initials: GT
authors.lastname: Chang
authors.forename: Bernhard
authors.initials: B
authors.lastname: Horsthemke
authors.forename: Tarik
authors.initials: T
authors.lastname: Möröy
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Lüdecke
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D017124:Conserved Sequence; D056445:Cytoplasmic Dyneins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000502:physiology; D006801:Humans; D051740:Ikaros Transcription Factor; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C108387:TRPS1 protein, human; D014157:Transcription Factors; D051740:Ikaros Transcription Factor; C427758:DYNLL1 protein, human; D056445:Cytoplasmic Dyneins; D004398:Dyneins