APPL Proteins Link Rab5 to Nuclear Signal Transduction via an Endosomal Compartment
| Autor: | Marino Zerial, Sandrine Uttenweiler-Joseph, Savvas Christoforidis, Angelika Giner, Marta Miaczynska, Bianca Habermann, Robert G. Parton, Anna Shevchenko, Matthias Wilm |
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| Přispěvatelé: | Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, European Molecular Biology Laboratory [Heidelberg] (EMBL), Institute for Molecular Bioscience, University of Queensland [Brisbane] |
| Rok vydání: | 2004 |
| Předmět: |
Plasma protein binding
Binding Sites/genetics Cell membrane Transduction (genetics) 0302 clinical medicine Endocytosis/*physiology Carrier Proteins/genetics/*metabolism Histone Deacetylases/genetics 0303 health sciences rab5 GTP-Binding Proteins/genetics/*metabolism Cell Division/genetics Endocytosis Cell biology Protein Transport Cell Compartmentation/genetics medicine.anatomical_structure Guanosine Triphosphate Signal transduction Proto-Oncogene Proteins Cell Division Protein Binding Signal Transduction Mi-2 Nucleosome Remodeling and Deacetylase Complex Cell Nucleus/*metabolism/ultrastructure Proto-Oncogene Proteins c-akt Endosome Endosomes Protein Serine-Threonine Kinases Biology Histone Deacetylases General Biochemistry Genetics and Molecular Biology Protein Binding/genetics Endosomes/*metabolism/ultrastructure 03 medical and health sciences Cell Membrane/*metabolism/ultrastructure medicine Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Protein-Serine-Threonine Kinases rab5 GTP-Binding Proteins 030304 developmental biology Cell Nucleus Binding Sites Biochemistry Genetics and Molecular Biology(all) Cell Membrane Protein Transport/genetics Cell Compartmentation Microscopy Electron Guanosine Triphosphate/metabolism Histone deacetylase complex Signal Transduction/genetics Carrier Proteins 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | Cell Cell, Elsevier, 2004, 116 (3), pp.445-456. ⟨10.1016/s0092-8674(04)00117-5⟩ ResearcherID |
| ISSN: | 0092-8674 1097-4172 |
| DOI: | 10.1016/s0092-8674(04)00117-5 |
| Popis: | International audience; Signals generated in response to extracellular stimuli at the plasma membrane are transmitted through cytoplasmic transduction cascades to the nucleus. We report the identification of a pathway directly linking the small GTPase Rab5, a key regulator of endocytosis, to signal transduction and mitogenesis. This pathway operates via APPL1 and APPL2, two Rab5 effectors, which reside on a subpopulation of endosomes. In response to extracellular stimuli such as EGF and oxidative stress, APPL1 translocates from the membranes to the nucleus where it interacts with the nucleosome remodeling and histone deacetylase multiprotein complex NuRD/MeCP1, an established regulator of chromatin structure and gene expression. Both APPL1 and APPL2 are essential for cell proliferation and their function requires Rab5 binding. Our findings identify an endosomal compartment bearing Rab5 and APPL proteins as an intermediate in signaling between the plasma membrane and the nucleus. |
| Databáze: | OpenAIRE |
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