The Leucine-Rich Repeat Region of CARMIL1 Regulates IL-1-Mediated ERK Activation, MMP Expression, and Collagen Degradation.
The Leucine-Rich Repeat Region of CARMIL1 Regulates IL-1-Mediated ERK Activation, MMP Expression, and Collagen Degradation.
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DOI：
10.1016/j.celrep.2020.107781
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发表时间：
2020-06-30
期刊：
影响因子：
8.8
通讯作者：
McCulloch CA
中科院分区：
文献类型：
--
作者：
Wang Q;Notay K;Downey GP;McCulloch CA
CARMILs are large, multidomain, membrane-associated proteins that regulate actin assembly and Rho-family GTPases, but their role in inflammatory signaling is not defined. Tandem mass tag mass spectrometry indicated that, in fibroblasts, CARMIL1 associates with interleukin (IL)-1 signaling molecules. Immunoprecipitation of cells transfected with CARMIL1 mutants showed that the leucine-rich repeat (LRR) region of CARMIL1 associates with IL-1 receptor type 1 (IL-1R1) and IL-1 receptor-associated kinase (IRAK). Knockout of CARMIL1 by CRISPR-Cas9 reduced IL-1-induced ERK activation by 72% and MMP3 expression by 40%. Compared with CARMIL1 wild-type (WT), cells expressing mutant CARMIL1 lacking its LRR domain exhibited 45% lower ERK activation and 40% lower MMP3 expression. In fibroblasts transduced with a cell-permeable, TAT CARMIL1 peptide that competed with IL-1R1 and IRAK binding to the LRR of CARMIL1, collagen degradation was reduced by 43%. As the LRR of CARMIL1 evidently regulates IL-1 signaling, CARMIL1 could become a target for anti-inflammatory drug development. CARMILs regulate actin assembly, but their role in inflammation is unknown. Wang et al. show that fibroblasts require CARMIL1 for IL-1 signaling. Knockout of CARMIL1 reduces IL-1 signaling and collagen degradation. Cell-permeable, CARMIL1-binding peptides that block its interaction with IL-1 signaling molecules inhibit collagen degradation. CARMIL1 is a promising target for anti-inflammatory drug development.
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DOI：
10.1073/pnas.1313738111
发表时间：
2014-05-13
影响因子：
11.1
作者：
Fujiwara, Ikuko;Remmert, Kirsten;Hammer, John A.
通讯作者：
Hammer, John A.
影响因子：
4.8
作者：
Burns, K;Martinon, F;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
4.8
作者：
Fujiwara, Ikuko;Remmert, Kirsten;Hammer, John A., III
通讯作者：
Hammer, John A., III
影响因子：
56.9
作者：
Muzio, M;Ni, J;Dixit, VM
通讯作者：
Dixit, VM
影响因子：
8.8
作者：
Coelho, Nuno M.;Arora, Pamma D.;McCulloch, Christopher A.
通讯作者：
McCulloch, Christopher A.