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Isoaspartylation appears to trigger small cell lung cancer-associated autoimmunity against neuronal protein ELAVL4.
Pulido, Mario A; DerHartunian, Meleeneh Kazarian; Qin, Zhenxia; Chung, Eric M; Kang, Diane S; Woodham, Andrew W; Tsou, Jeffrey A; Klooster, Rinse; Akbari, Omid; Wang, Lina; Kast, W Martin; Liu, Stephen V; Verschuuren, Jan J G M; Aswad, Dana W; Laird-Offringa, Ite A.
Afiliación
  • Pulido MA; Departments of Surgery and of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • DerHartunian MK; Departments of Surgery and of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Qin Z; Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA.
  • Chung EM; Departments of Surgery and of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Kang DS; Departments of Surgery and of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Woodham AW; Department of Molecular Microbiology and Immunology Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Tsou JA; Departments of Surgery and of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Klooster R; Departments of Surgery and of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Akbari O; Department of Molecular Microbiology and Immunology Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Wang L; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Kast WM; Department of Molecular Microbiology and Immunology Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Liu SV; Department of Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Verschuuren JJGM; Department of Neurology, Leiden University, Leiden, the Netherlands.
  • Aswad DW; Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA.
  • Laird-Offringa IA; Departments of Surgery and of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
J Neuroimmunol ; 299: 70-78, 2016 10 15.
Article en En | MEDLINE | ID: mdl-27725125
ABSTRACT
Autoantibodies against SCLC-associated neuronal antigen ELAVL4 (HuD) have been linked to smaller tumors and improved survival, but the antigenic epitope and mechanism of autoimmunity have never been solved. We report that recombinant human ELAVL4 protein incubated under physiological conditions acquires isoaspartylation, a type of immunogenic protein damage. Specifically, the N-terminal region of ELAVL4, previously implicated in SCLC-associated autoimmunity, undergoes isoaspartylation in vitro, is recognized by sera from anti-ELAVL4 positive SCLC patients and is highly immunogenic in subcutaneously injected mice and in vitro stimulated human lymphocytes. Our data suggest that isoaspartylated ELAVL4 is the trigger for the SCLC-associated anti-ELAVL4 autoimmune response.
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Texto completo: 1 Colección: 01-internacional Asunto principal: Autoinmunidad / Carcinoma Pulmonar de Células Pequeñas / Proteína 4 Similar a ELAV / Neoplasias Pulmonares / Neuronas Tipo de estudio: Risk_factors_studies Límite: Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: J Neuroimmunol Año: 2016 Tipo del documento: Article País de afiliación: Canadá

Texto completo: 1 Colección: 01-internacional Asunto principal: Autoinmunidad / Carcinoma Pulmonar de Células Pequeñas / Proteína 4 Similar a ELAV / Neoplasias Pulmonares / Neuronas Tipo de estudio: Risk_factors_studies Límite: Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: J Neuroimmunol Año: 2016 Tipo del documento: Article País de afiliación: Canadá