In vivo genetic mutations define predominant functions of the human T-cell leukemia/lymphoma virus p12I protein
| Autor: | Genoveffa Franchini, Julie M. Nauroth, Valentina Cecchinato, Izabela Bialuk, Vibeke Andresen, Jean Claude Walser, Antoine Gessain, Christophe Nicot, Valerio W. Valeri, Risaku Fukumoto |
|---|---|
| Přispěvatelé: | Animal Models and Retroviral Vaccines Section, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Section on Genomic Structure and Function, National Institute of Diabetes and Digestive and Kidney Diseases [Bethesda], Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Microbiology, Molecular genetics and Immunology, University of Kansas Medical Center [Lawrence], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Kansas Medical Center [Kansas City, KS, USA] |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Immunological Synapses
Calnexin viruses Golgi Apparatus Biochemistry Jurkat cells MESH: Histocompatibility Antigens Class I Jurkat Cells 0302 clinical medicine Chlorocebus aethiops MESH: Jurkat Cells Viral Regulatory and Accessory Proteins MESH: Animals Immunologic Capping Cellular localization Human T-lymphotropic virus 1 0303 health sciences biology MESH: Receptors Antigen T-Cell Hematology Cell biology MESH: COS Cells MESH: Interleukin-2 Receptor beta Subunit Protein Transport medicine.anatomical_structure [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology MESH: Cell Survival 030220 oncology & carcinogenesis COS Cells MESH: Membrane Proteins Signal transduction MESH: Protein Sorting Signals Hydrophobic and Hydrophilic Interactions MESH: Viral Regulatory and Accessory Proteins Interleukin Receptor Common gamma Subunit Protein Binding MESH: Protein Transport MESH: Mutation Cell Survival MESH: Calreticulin T cell Immunology Receptors Antigen T-Cell Protein Sorting Signals 03 medical and health sciences MESH: Golgi Apparatus MESH: Immunological Synapses MESH: Cell Proliferation MESH: HTLV-I Infections medicine Animals Humans MESH: Protein Binding MESH: Calnexin Cell Proliferation Immunobiology 030304 developmental biology MESH: Hydrophobicity MESH: Human T-lymphotropic virus 1 MESH: Humans MESH: Interleukin Receptor Common gamma Subunit Endoplasmic reticulum Histocompatibility Antigens Class I T-cell receptor MESH: Immunologic Capping Membrane Proteins Cell Biology HTLV-I Infections Virology MESH: Cercopithecus aethiops Interleukin-2 Receptor beta Subunit MESH: Hela Cells Mutation biology.protein Calreticulin HeLa Cells 030215 immunology |
| Zdroj: | Blood Blood, American Society of Hematology, 2009, 113 (16), pp.3726-34. ⟨10.1182/blood-2008-04-146928⟩ Blood, 2009, 113 (16), pp.3726-34. ⟨10.1182/blood-2008-04-146928⟩ |
| ISSN: | 0006-4971 1528-0020 |
| Popis: | The human T-cell leukemia/lymphoma virus Type 1 (HTLV-1) ORF-I encodes, a ninety-nine amino acid hydrophobic membrane protein, p12I that affects receptors in different cellular compartments. We report here that proteolytic cleavage dictates different cellular localization and functions of p12I. The removal of a non-canonical endoplasmic reticulum (ER) retention/retrieval signal within the amino terminus of p12I is necessary for trafficking to the Golgi apparatus and generation of a completely cleaved 8 kDa protein. The 8 kDa protein in turn traffics to the cell surface, is recruited to the immunological synapse following T-cell receptor (TCR) ligation and down-regulates TCR proximal signaling. The uncleaved 12 kDa form of p12I resides in the ER and interacts with the β and γc chains of the interleukin-2 receptor (IL-2R), the heavy chain of the major histocompatibility complex (MHC) class I, as well as calreticulin and calnexin. Genetic analysis of ORF-I from ex vivo samples of HTLV-1-infected patients reveals predominant amino acid substitutions within ORF-I that inhibits proteolytic cleavage, suggesting that ER associated functions of p12I may contribute to the survival and proliferation of the infected T-cells in the host. |
| Databáze: | OpenAIRE |
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