Absence of Cytosolic 2-Cys Prx Subtypes I and II Exacerbates TNF-alpha-Induced Apoptosis via Different Routes
- 주제(기타) Cell Biology
- 설명문(일반) [Lee, Sunmi; Lee, Joo Young; Park, Sujin; Kang, Dong Hoon; Min, Chengchun; Lee, Doo Jae; Kang, Dongmin; Kwon, Jongbum; Kang, Sang Won] Ewha Womans Univ, Dept Life Sci, Seoul 03760, South Korea; [Lee, Sunmi; Kang, Dong Hoon; Min, Chengchun; Lee, Doo Jae; Kwon, Jongbum; Kang, Sang Won] Ewha Womans Univ, Res Ctr Cell Homeostasis, Seoul 03760, South Korea; [Lee, Eun Woo] Korea Res Inst Biosci & Biotechnol, Metab Regulat Res Ctr, Daejeon 34141, South Korea; [Song, Jaewhan] Yonsei Univ, Dept Biochem, Seoul 03722, South Korea; [Lee, Joo Young] Yonsei Univ, Coll Med, Dept Severance Biomed Sci Inst, Seoul 03722, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold
- 발행기관 CELL PRESS
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000159944
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.celrep.2019.01.081
- PubMed https://pubmed.ncbi.nlm.nih.gov/30784599
초록/요약
There are abundant peroxiredoxin (Prx) enzymes, but an increase of cellular H2O2 level always happens in apoptotic cells. Here, we show that cellular H2O2 switches different apoptosis pathways depending on which type of Prx enzyme is absent. TNF alpha-induced H2O2 burst preferentially activates the DNA damage-dependent apoptosis pathway in the absence of PrxI. By contrast, the same H2O2 burst stimulates the RIPK1-dependent apoptosis pathway in the absence of PrxII by inducing the destruction of cIAP1 in caveolar membrane. Specifically, H2O2 induces the oxidation of Cys308 residue in the cIAP1-BIR3 domain, which induces the dimerization-dependent E3 ligase activation. Thus, the reduction in cIAP level by the absence of PrxII triggers cell-autonomous apoptosis in cancer cells and tumors. Such differential functions of PrxI and PrxII are mediated by interaction with H2AX and cIAP1, respectively. Collectively, this study reveals the distinct switch roles of 2-Cys Prx isoforms in apoptosis signaling.
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