title: Heterogeneous nuclear ribonuclear protein U associates with YAP and regulates its co-activation of Bax transcription.
abstract: Although initially described as a cytosolic scaffolding protein, YAP (Yes-associated protein of 65 kDa) is known to associate with multiple transcription factors in the nucleus. Using affinity chromatography and mass spectrometry, we show that YAP interacts with heterogeneous nuclear ribonuclear protein U (hnRNP U), an RNA- and DNA-binding protein enriched in the nuclear matrix that also plays a role in the regulation of gene expression. hnRNP U interacts specifically with the proline-rich amino terminus of YAP, a region of YAP that is not found in the related protein TAZ. Although hnRNP U and YAP localize to both the nucleus and the cytoplasm, YAP does not translocate to the nucleus in an hnRNP U-dependent manner. Furthermore, hnRNP U and YAP only interact in the nucleus, suggesting that the association between the two proteins is regulated. Co-expression of hnRNP U attenuates the ability of YAP to increase the activity of a p73-driven Bax-luciferase reporter plasmid. In contrast, hnRNP U has no effect when co-expressed with a truncated YAP protein lacking the hnRNP U-binding site. Because YAP is distinguished from the homologue TAZ by its proline-rich amino terminus, the YAP-hnRNP U interaction may uniquely regulate the nuclear function(s) of YAP. The YAP-hnRNP U interaction provides another mechanism of YAP transcriptional regulation.
authors.affiliation: Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Howell
authors.forename: Christoph
authors.initials: C
authors.lastname: Borchers
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Milgram
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D002846:Chromatography, Affinity; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D034722:Heterogeneous-Nuclear Ribonucleoprotein U / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011392:Proline / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D034722:Heterogeneous-Nuclear Ribonucleoprotein U; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015534:Trans-Activators; D014157:Transcription Factors; C456659:YY1AP1 protein, human; D051028:bcl-2-Associated X Protein; D011392:Proline; D008156:Luciferases