Dachshund (Dac) is a highly conserved nuclear protein that is distantly related to the Ski/Sno family of corepressor proteins. In Drosophila, Dac is necessary and sufficient for eye development and, along with Eyeless (Ey), Sine oculis (So), and Eyes absent (Eya), forms the core of the retinal determination (RD) network. In vivo and in vitro experiments suggest that members of the RD network function together in one or more complexes to regulate the expression of downstream targets. For example, Dac and Eya synergize in vivo to induce ectopic eye formation and they physically interact through conserved domains. Dac contains two highly conserved domains, named DD1 and DD2, but no function has been assigned to either of them in an in vivo context. We performed structure-function studies to understand the relationship between the conserved domains of Dac and the rest of the protein and to determine the function of each domain during development. We show that only DD1 is essential for Dac function and while DD2 facilitates DD1, it is not absolutely essential in spite of more than 500 million years of conservation. Moreover, the physical interaction between Eya and DD2 is not required for the genetic synergy between the two proteins. Finally, we show that DD1 also plays a central role for nuclear localization of Dac.
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http://dx.doi.org/10.1016/j.ydbio.2004.05.005 | DOI Listing |
Ann Surg Oncol
January 2025
Department of Surgery, School of Medicine and Public Health, Wisconsin Surgical Outcomes Research Program, University of Wisconsin, Madison, WI, USA.
Introduction: Little is known about the symptom burden of breast cancer survivors with early-stage disease. Many studies have focused on symptoms of patients who are undergoing or recently completed systemic therapy. However, with the increased use of Oncotype DX, the proportion of early-stage hormone receptor-positive patients who undergo chemotherapy has declined, making existing studies of the symptom experience less useful for these patients.
View Article and Find Full Text PDFNature
January 2025
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Caspase recruitment domains (CARDs) and pyrin domains are important facilitators of inflammasome activity and pyroptosis. Following pathogen recognition by nucleotide binding-domain, leucine-rich, repeat-containing (NLR) proteins, CARDs recruit and activate caspases, which, in turn, activate gasdermin pore-forming proteins to induce pyroptotic cell death. Here we show that CARD domains are present in defence systems that protect bacteria against phage.
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January 2025
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM Juriquilla, Querétaro, Querétaro, Mexico. Electronic address:
fos genes, transcription factors with a common basic region and leucine zipper domains binding to a consensus DNA sequence (TGA{}TCA), are evolutionarily conserved in eukaryotes. Homologs can be found in many different species from yeast to vertebrates. In yeast, the homologous GCN4 gene is required to mediate "emergency" situations like nutrient deprivation and the unfolded protein response.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4K1; Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada L8S 4K1. Electronic address:
Type VI secretion systems (T6SS) are dynamic protein nanomachines found in Gram-negative bacteria that deliver toxic effector proteins into target cells in a contact-dependent manner. Prior to secretion, many T6SS effector proteins require chaperones and/or accessory proteins for proper loading onto the structural components of the T6SS apparatus. However, despite their established importance, the precise molecular function of several T6SS accessory protein families remains unclear.
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January 2025
Institute for Ophthalmic Research, Center for Ophthalmology, University of Tübingen, Elfriede-Aulhorn-Strasse 7, 72076 Tübingen, Germany. Electronic address:
Genotype-phenotype correlations of rare diseases are complicated by low patient number, high phenotype variability and compound heterozygosity. Mutations may cause instability of single proteins, and affect protein complex formation or overall robustness of a specific process in a given cell. Ciliopathies offer an interesting case for studying genotype-phenotype correlations as they have a spectrum of severity and include diverse phenotypes depending on different mutations in the same protein.
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