Kei Miyano
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Natural Sciences,
   Position   Assistant Professor
Article types 原著
Language English
Peer review Peer reviewed
Title Characterization of missense mutations in the NADPH oxidase partner p22phox in the A22° subtype of chronic granulomatous disease.
Journal Formal name：Microbiology and immunology
Domestic / ForeginForegin
Publisher Wiley
Volume, Issue, Page 67(4),pp.194-200
Author and coauthor Kawai, C., Kajikawa, M., Yamauchi, A., Okamoto, S., Kuribayashi, F., & Miyano, K.
Authorship Last author,Corresponding author
Publication date 2023/01/06
Summary Defective superoxide production by NADPH oxidase 2 (Nox2) in phagocyte cells results in the development of chronic granulomatous disease (CGD), a hereditary disease characterized by recurrent and life-threatening infections. The partner protein p22phox is a membrane-spanning protein which forms a stable heterodimer with Nox2 in the endoplasmic reticulum. This interaction ensures the stability of each protein and their accurate trafficking to the cell membrane. The present paper describes the characterization of p22phox missense mutations that were identified in a patient with CGD who presented with undetectable levels of p22phox . Using a reconstitution system, it was found that p22phox expression decreased when R90Q, A117E, S118R, A124S, A124V, A125T, or E129K mutations were introduced, suggesting that these mutations destabilize the protein. In contrast, introducing an L105R mutation did not affect protein expression, but did inhibit p22phox binding to Nox2. Thus, the missense mutations discussed here contribute to the development of CGD by either disrupting protein stability or by impairing the interaction between p22phox and Nox2.
DOI 10.1111/1348-0421.13051
PMID 36606663
URL for researchmap https://onlinelibrary.wiley.com/doi/10.1111/1348-0421.13051