BROWSE

Related Scientist

Researcher

RNA 연구단
RNA 연구단
more info

A central role for PI3K-AKT signaling pathway in linking SAMHD1-deficiency to the type I interferon signature

Cited 4 time in webofscience Cited 0 time in scopus
210 Viewed 92 Downloaded
Title
A central role for PI3K-AKT signaling pathway in linking SAMHD1-deficiency to the type I interferon signature
Author(s)
Changhoon Oh ; Jeongmin Ryoo; Park, K; Kim, B; Daly, MB; DongYeon Cho ; Kwangseog Ahn
Publication Date
2018-01
Journal
SCIENTIFIC REPORTS, v.8, no., pp.84 -
Publisher
NATURE PUBLISHING GROUP
Abstract
The autoimmune disorder Aicardi-Goutieres syndrome (AGS) is characterized by a constitutive type I interferon response. SAMHD1 possesses both dNTPase and RNase activities and mutations in SAMHD1 cause AGS; however, how SAMHD1-deficiency causes the type I interferon response in patients with AGS remains unknown. Here, we show that endogenous RNA substrates accumulated in the absence of SAMHD1 act as a major immunogenic source for the type I interferon response. Reconstitution of SAMHD1-negative human cells with wild-type but not RNase-defective SAMHD1 abolishes spontaneous type I interferon induction. We further identify that the PI3K/AKT/IRF3 signaling pathway is essential for the type I interferon response in SAMHD1-deficient human monocytic cells. Treatment of PI3K or AKT inhibitors dramatically reduces the type I interferon signatures in SAMHD1-deficient cells. Moreover, SAMHD1/AKT1 double knockout relieves the type I interferon signatures to the levels observed for wild-type cells. Identification of AGS-related RNA sensing pathway provides critical insights into the molecular pathogenesis of the type I interferonopathies such as AGS and overlapping autoimmune disorders. © The Author(s) 2017
URI
http://pr.ibs.re.kr/handle/8788114/4455
DOI
10.1038/s41598-017-18308-8
ISSN
2045-2322
Appears in Collections:
Center for RNA Research(RNA 연구단) > Journal Papers (저널논문)
Files in This Item:
s41598-017-18308-8 (1).pdfDownload

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse