γ-secretase fanning the fire of innate immunity Review


Authors: Liu, C.; Nikain, C.; Li, Y. M.
Review Title: γ-secretase fanning the fire of innate immunity
Abstract: Innate immunity is the first line of defense against pathogens, alerting the individual cell and surrounding area to respond to this potential invasion. γ-secretase is a transmembrane protease complex that plays an intricate role in nearly every stage of this innate immune response. Through regulation of pattern recognition receptors (PRR) such as TREM2 and RAGE γ-secretase can modulate pathogen recognition. γ-secretase can act on cytokine receptors such as IFNαR2 and CSF1R to dampen their signaling capacity. While γ-secretase-mediated regulated intramembrane proteolysis (RIP) can further moderate innate immune responses through downstream signaling pathways. Furthermore, γ-secretase has also been shown to be regulated by the innate immune system through cytokine signaling and γ-secretase modulatory proteins such as IFITM3 and Hif-1α. This review article gives an overview of how γ-secretase is implicated in innate immunity and the maintenance of its responses through potentially positive and negative feedback loops. © 2023 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
Keywords: signal transduction; metabolism; inflammation; innate immunity; immunity, innate; regulated intramembrane proteolysis; amyloid precursor protein secretases; secretase; cytokine signaling; ifitm3; hif1a
Journal Title: Biochemical Society Transactions
Volume: 51
Issue: 4
ISSN: 0300-5127
Publisher: Portland Press Ltd  
Date Published: 2023-08-01
Start Page: 1597
End Page: 1610
Language: English
DOI: 10.1042/bst20221445
PUBMED: 37449907
PROVIDER: scopus
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Yue-Ming Li -- Source: Scopus
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MSK Authors
  1. Yueming Li
    132 Li
  2. Chenge Liu
    2 Liu
  3. Cyrus Nikain
    2 Nikain