이기영 (성균관대학교 의과대학) | 한빛사논문 > 한빛사

한빛사논문

조회2,554

성균관대학교 의과대학

CV File 385 kb

Autophagy, Accepted author version posted online: 21 Jun 2018 | https://doi.org/10.1080/15548627.2018.1474995 Inhibition of TRAF6 ubiquitin-ligase activity by PRDX1 leads to inhibition of NFKB activation and autophagy activation

Yoon Min¹, Mi-Jeong Kim¹, Sena Lee¹, Eunyoung Chun^2,*, & Ki-Young Lee^1,3,4,*

¹Department of Molecular Cell Biology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea
²Department of Immunology and Infectious Diseases, Harvard School of Public Health, and the Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
³Samsung Medical Center, Seoul 06351, Korea;
⁴Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Samsung Medical Center, Sungkyunkwan University, Seoul 06351, Korea

^*Correspondence

Abstract

TRAF6 (TNF receptor associated factor 6) plays a pivotal role in NFKB activation and macroautphagy/autophagy activation induced by TLR4 (toll like receptor 4) signaling. The objective of this study was to determine the functional role of PRDX1 (peroxiredoxin 1) in NFKB activation and autophagy activation. PRDX1 interacted with the ring finger domain of TRAF6 and inhibited its ubiquitin-ligase activity. The inhibition on TRAF6 ubiquitin-ligase activity by PRDX1 induced the suppression of ubiquitination of an evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) essential for NFKB activation and BECN1 (beclin 1) required for autophagy activation. An inhibitory effect of PRDX1 on TRAF6 was clearly evidenced in PRDX1-knockdown (PRDX1KD) THP-1, PRDX1KD MDA-MB-231, and PRDX1KD SK-HEP-1 cells. PRDX1KD THP-1 cells showed increases of NFKB activation, pro-inflammatory cytokine production, NFKB-dependent gene expression induced by TLR4 stimulation, and resistance against Salmonella typhimurium infection. Additionally, migration and invasion abilities of PRDX1KD MDA-MB-231 and PRDX1KD SK-HEP-1 cancer cells were significantly enhanced compared to those of control cancer cells. Taken together, these results suggest that PRDX1 negatively regulates TLR4 signaling for NFKB activation and autophagy functions such as bactericidal activity, cancer cell migration, and cancer cell invasion by inhibiting TRAF6 ubiquitin-ligase activity.

Keywords: autophagy, peroxiredoxin1, toll like receptor 4, TRAF6, ubiquitination

논문정보

형식Research article
게재일2018년 06월 (BRIC 등록일 2018-07-17)
연구진국내(교신)+국외 연구진
분야 의약학 > 면역의학

댓글 작성 로그인

CV 열람하기

연락처 보기