TY - JOUR
T1 - Nuclear interaction of the dynein light chain LC8a with the TRPS1 transcription factor suppresses the transcriptional repression activity of TRPS1
AU - Kaiser, Frank J.
AU - Tavassoli, Kamiab
AU - Van den Bemd, Gert Jan
AU - Chang, Glenn T.G.
AU - Horsthemke, Bernhard
AU - Möröy, Tarik
AU - Lüdecke, Hermann Josef
N1 - Funding Information:
We thank R. Shivdasani for providing the XGATA4 and the luciferase reporter (aD3) constructs, Diane von Holtum, Stephanie Groß and Mila Jhamai for expert technical assistance, and Albert O. Brinkmann for continuous support. This work was supported by the Deutsche Forschungsgemeinschaft (Lu483/5-1) and by the Association for International Cancer Research (AICR00-506).
PY - 2003/6/1
Y1 - 2003/6/1
N2 - 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 C2H2 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.
AB - 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 C2H2 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.
UR - http://www.scopus.com/inward/record.url?scp=0038006754&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddg145
DO - 10.1093/hmg/ddg145
M3 - Journal articles
C2 - 12761050
AN - SCOPUS:0038006754
SN - 0964-6906
VL - 12
SP - 1349
EP - 1358
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 11
ER -
