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한빛사논문

조회373

남영우Young Woo Nam

연세대학교

Cell Death Differ., May 24 2024, | https://doi.org/10.1038/s41418-024-01316-3 EGFR inhibits TNF-α-mediated pathway by phosphorylating TNFR1 at tyrosine 360 and 401

Young Woo Nam¹, June-Ha Shin¹, Seongmi Kim¹, Chi Hyun Hwang¹, Choong-Sil Lee¹, Gyuho Hwang¹, Hwa-Ryeon Kim¹, Jae-Seok Roe¹and Jaewhan Song¹

¹Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.

Corresponding author

Correspondence to Jaewhan Song.

Abstract

Tumour necrosis factor receptor 1 (TNFR1) induces the nuclear factor kappa-B (NF-κB) signalling pathway and regulated cell death processes when TNF-α ligates with it. Although mechanisms regulating the downstream pathways of TNFR1 have been elucidated, the direct regulation of TNFR1 itself is not well known. In this study, we showed that the kinase domain of the epidermal growth factor receptor (EGFR) regulates NF-κB signalling and TNF-α-induced cell death by directly phosphorylating TNFR1 at Tyr 360 and 401 in its death domain. In contrast, EGFR inhibition by EGFR inhibitors, such as erlotinib and gefitinib, prevented their interaction. Once TNFR1 is phosphorylated, its death domain induces the suppression of the NF-κB pathways, complex II-mediated apoptosis, or necrosome-dependent necroptosis. Physiologically, in mouse models, EGF treatment mitigates TNF-α-dependent necroptotic skin inflammation induced by treatment with IAP and caspase inhibitors. Our study revealed a novel role for EGFR in directly regulating TNF-α-related pathways.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-27)
연구진국내 연구진
분야 생명과학 > 노화/암생물학

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