The Y‐box factor ZONAB/DbpA associates with GEF‐H1/Lfc and mediates Rho‐stimulated transcription
Autor: | Maria S. Balda, Saima Aijaz, Karl Matter, Isabelle V. Leefa Chong San, Mei Nie |
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Rok vydání: | 2009 |
Předmět: |
tight junctions
RHOA Transcription Genetic proliferation Scientific Report Active Transport Cell Nucleus cyclin D1 GTPase Biology Biochemistry DNA-binding protein Cell Line 03 medical and health sciences Dogs 0302 clinical medicine Cyclin D1 Rho GTPases TNFα Genetics Animals Guanine Nucleotide Exchange Factors Molecular Biology Transcription factor 030304 developmental biology 0303 health sciences Activator (genetics) Molecular biology Cell biology DNA-Binding Proteins Gene Expression Regulation 030220 oncology & carcinogenesis biology.protein Guanine nucleotide exchange factor Signal transduction Rho Guanine Nucleotide Exchange Factors Protein Binding Signal Transduction Transcription Factors |
Zdroj: | EMBO Reports |
ISSN: | 1469-3178 1469-221X |
Popis: | Epithelial tight junctions recruit different types of signalling proteins that regulate cell proliferation and differentiation. Little is known about how such proteins interact functionally and biochemically with each other. Here, we focus on the Y-box transcription factor ZONAB (zonula occludens 1-associated nucleic-acid-binding protein)/DbpA (DNA-binding protein A) and the Rho GTPase activator guanine nucleotide exchange factor (GEF)-H1/Lbc's first cousin, which are two tight-junction-associated signalling proteins that regulate proliferation. Our data show that the two proteins interact and that ZONAB activity is Rho-dependent. Overexpression of GEF-H1 induces accumulation of ZONAB in the nucleus and activates transcription. Microtubule-affinity regulating kinase/partition-defective-1, another type of GEF-H1-associated signalling protein, remains in the cytoplasm and partially co-localizes with the exchange factor. GEF-H1 and ZONAB are required for expression of endogenous cyclin D1, a crucial RhoA signalling target gene, and GEF-H1-stimulated cyclin D1 promoter activity requires ZONAB. Our data thus indicate that GEF-H1 and ZONAB form a signalling module that mediates Rho-regulated cyclin D1 promoter activation and expression. |
Databáze: | OpenAIRE |
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