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Title: The GAR/RGG motif defines a family of nuclear alarmins
Authors: Wu, Shan
Teo, Boon Heng Dennis 
Wee, Seng Yin Kelly
Chen, Junjie 
Lu, Jinhua 
Issue Date: 1-May-2021
Publisher: Springer Nature
Citation: Wu, Shan, Teo, Boon Heng Dennis, Wee, Seng Yin Kelly, Chen, Junjie, Lu, Jinhua (2021-05-01). The GAR/RGG motif defines a family of nuclear alarmins. Cell Death and Disease 12 (5) : 477. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: The nucleus is the target of autoantibodies in many diseases, which suggests intrinsic nuclear adjuvants that confer its high autoimmunogenicity. Nucleolin (NCL) is one abundant nucleolar autoantigen in systemic lupus erythematosus (SLE) patients and, in lupus-prone mice, it elicits autoantibodies early. With purified NCL, we observed that it was a potent alarmin that activated monocytes, macrophages and dendritic cells and it was a ligand for TLR2 and TLR4. NCL released by necrotic cells also exhibited alarmin activity. The NCL alarmin activity resides in its glycine/arginine-rich (GAR/RGG) motif and can be displayed by synthetic GAR/RGG peptides. Two more GAR/RGG-containing nucleolar proteins, fibrillarin (FBRL) and GAR1, were also confirmed to be novel alarmins. Therefore, the GAR/RGG alarmin motif predicts a family of nucleolar alarmins. The apparent prevalence of nucleolar alarmins suggests their positive contribution to tissue homeostasis by inducing self-limiting tissue inflammation with autoimmunity only occurring when surveillance is broken down. © 2021, The Author(s).
Source Title: Cell Death and Disease
ISSN: 2041-4889
DOI: 10.1038/s41419-021-03766-w
Rights: Attribution 4.0 International
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