Autoantibodies to DNA-dependent protein kinase probes for the catalytic subunit

Akira Suwa, Michito Hirakata, Yoshihiko Takeda, Yutaka Okano, Tsuneyo Mimori, Shinichi Inada, Fumiaki Watanabe, Hirobumi Teraoka, William S. Dynan, John A. Hardin

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Abstract

DNA-dependent protein kinase (DNA-PK) is an important nuclear enzyme which consists of a catalytic subunit known as DNA-PKcs and a regulatory component identified as the Ku autoantigen. In the present study, we surveyed 312 patients in a search for this specificity. 10 sera immunoprecipitated a large polypeptide which exactly comigrated with DNA-PKcs in SDS-PAGE. Immunoblot analysis demonstrated that this polypeptide was recognizable by a rabbit antiserum specific for DNA-PKcs. Although the patient sera did not bind to biochemically purified DNA-PKcs in immunoblots or ELISA, they were able to deplete DNA-PK catalytic activity from extracts of HeLa cells in a dose-dependent manner. We conclude that these antibodies should be useful probes for studies which aim to define the role of DNA-PK in cells. Since six sera simultaneously contained antibodies to the Ku protein, these studies suggest that relatively intact forms of DNA-PK complex act as autoantigenic particles in selected patients.

Original languageEnglish
Pages (from-to)1417-1421
Number of pages5
JournalJournal of Clinical Investigation
Volume97
Issue number6
DOIs
Publication statusPublished - 1996 Mar 15

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Keywords

  • Antinuclear antibodies
  • Autoantibodies
  • Autoimmunity
  • DNA-dependent protein kinase
  • Ku protein

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Suwa, A., Hirakata, M., Takeda, Y., Okano, Y., Mimori, T., Inada, S., Watanabe, F., Teraoka, H., Dynan, W. S., & Hardin, J. A. (1996). Autoantibodies to DNA-dependent protein kinase probes for the catalytic subunit. Journal of Clinical Investigation, 97(6), 1417-1421. https://doi.org/10.1172/JCI118562