title: NLRP7, Involved in Hydatidiform Molar Pregnancy (HYDM1), Interacts with the Transcriptional Repressor ZBTB16.
abstract: Mutations in the maternal effect gene NLRP7 cause biparental hydatidiform mole (HYDM1). HYDM1 is characterized by abnormal growth of placenta and lack of proper embryonic development. The molar tissues are characterized by abnormal methylation patterns at differentially methylated regions (DMRs) of imprinted genes. It is not known whether this occurs before or after fertilization, but the high specificity of this defect to the maternal allele indicates a possible maternal germ line-specific effect. To better understand the unknown molecular mechanism leading to HYDM1, we performed a yeast two-hybrid screen against an ovarian library using NLRP7 as bait. We identified the transcriptional repressor ZBTB16 as an interacting protein of NLRP7 and verified this interaction in mammalian cells by immunoprecipitation and confocal microscopy. Native protein analysis detected NLRP7 and ZBTB16 in a 480kD protein complex and both proteins co-localize in the cytoplasm in juxtanuclear aggregates. HYDM1-causing mutations in NLRP7 did not show altered patterns of interaction with ZBTB16. Hence, the biological significance of the NLRP7-ZBTB16 interaction remains to be revealed. However, a clear effect of harvesting ZBTB16 to the cytoplasm when the NLRP7 protein is overexpressed may be linked to the pathology of the molar pregnancy disease.
authors.affiliation: Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Bonn, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Singer
authors.affiliation: Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Bonn, Germany.
authors.forename: Arijit
authors.initials: A
authors.lastname: Biswas
authors.affiliation: Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Bonn, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Nuesgen
authors.affiliation: Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Bonn, Germany.
authors.forename: Osman
authors.initials: O
authors.lastname: El-Maarri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000483:Alleles; D003593:Cytoplasm / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D015723:Gene Library; D057809:HEK293 Cells; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000502:physiology; D008297:Male; D018613:Microscopy, Confocal; D009154:Mutation; D010053:Ovary / Q000378:metabolism; D011247:Pregnancy; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D020798:Two-Hybrid System Techniques
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051741:Kruppel-Like Transcription Factors; C502448:NLRP7 protein, human; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C092037:ZBTB16 protein, human