Direct role of Bardet–Biedl syndrome proteins in transcriptional regulation
| Autor: | Cecilia Gascue, Soledad Astrada, Yangfan P. Liu, Jose L. Badano, Nicholas Katsanis, Tamara Fernández-Calero, Carlos Robello, Gabriela Libisch, Magdalena Cardenas-Rodriguez, Hugo Naya, Perciliz L. Tan |
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| Přispěvatelé: | Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP), Center for Human Disease Modeling, Duke University [Durham], Departamento de Bioquimica, Facultad de Medicina- Universidad de la República [Montevideo] (UCUR), This study was supported by the Agencia Nacional de Investigacion e Innovacio'n (ANII-Innova) and Fondo Clemente Estable (FCE) [grant number PR_FCE_2009_1_2382 to J.L.B.], by the National Institute of Child Health and Development [grant number R01HD04260 to J.K.], and by the National Institute of Diabetes, Digestive and Kidney disorders, National Institutes of Health [grant numbers R01DK072301, R01DK075972 to N.K.]. J.L.B. is supported by the Genzyme Renal Innovations Program (GRIP). J.L.B., C.G., G.L., M.C.-R., S.A., C.R. and H.N. are supported by the 'Programa de Desarrollo de las Ciencias Basicas (PEDECIBA), and by ANIIInnova, Uruguay. N.K. is a Distinguished Brumley Professor. |
| Rok vydání: | 2012 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Transcription Genetic [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Ciliopathies BBS Mice 03 medical and health sciences 0302 clinical medicine Bardet–Biedl syndrome medicine Animals Humans Basal body Computer Simulation Polycomb group Cilia Nuclear export signal Zebrafish Research Articles Tissue homeostasis Adaptor Proteins Signal Transducing 030304 developmental biology Cell Nucleus Nuclear Export Signals Polycomb Repressive Complex 1 Genetics [SDV.GEN]Life Sciences [q-bio]/Genetics 0303 health sciences Cilium Proteins Cell Biology medicine.disease [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] Transport protein Cell biology Cytoskeletal Proteins Protein Transport Ciliopathy HEK293 Cells Gene Expression Regulation NIH 3T3 Cells [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | Journal of Cell Science Journal of Cell Science, Company of Biologists, 2012, 125 (Pt 2), pp.362-75. ⟨10.1242/jcs.089375⟩ |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.089375 |
| Popis: | International audience; Primary cilia are conserved organelles that play crucial roles as mechano- and chemosensors, as well as transducing signaling cascades. Consequently, ciliary dysfunction results in a broad range of phenotypes: the ciliopathies. Bardet-Biedl syndrome (BBS), a model ciliopathy, is caused by mutations in 16 known genes. However, the biochemical functions of the BBS proteins are not fully understood. Here we show that the BBS7 protein (localized in the centrosomes, basal bodies and cilia) probably has a nuclear role by virtue of the presence of a biologically confirmed nuclear export signal. Consistent with this observation, we show that BBS7 interacts physically with the polycomb group (PcG) member RNF2 and regulate its protein levels, probably through a proteasome-mediated mechanism. In addition, our data supports a similar role for other BBS proteins. Importantly, the interaction with this PcG member is biologically relevant because loss of BBS proteins leads to the aberrant expression of endogenous RNF2 targets in vivo, including several genes that are crucial for development and for cellular and tissue homeostasis. Our data indicate a hitherto unappreciated, direct role for the BBS proteins in transcriptional regulation and potentially expand the mechanistic spectrum that underpins the development of ciliary phenotypes in patients. |
| Databáze: | OpenAIRE |
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