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Absence of Cytosolic 2-Cys Prx Subtypes I and II Exacerbates TNF-α-Induced Apoptosis via Different Routes.
Lee, Sunmi; Lee, Joo Young; Lee, Eun Woo; Park, Sujin; Kang, Dong Hoon; Min, Chengchun; Lee, Doo Jae; Kang, Dongmin; Song, Jaewhan; Kwon, Jongbum; Kang, Sang Won.
Affiliation
  • Lee S; Department of Life Science, Ewha Womans University, Seoul 03760, Korea; Research Center for Cell Homeostasis, Ewha Womans University, Seoul 03760, Korea.
  • Lee JY; Department of Life Science, Ewha Womans University, Seoul 03760, Korea.
  • Lee EW; Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea.
  • Park S; Department of Life Science, Ewha Womans University, Seoul 03760, Korea.
  • Kang DH; Department of Life Science, Ewha Womans University, Seoul 03760, Korea; Research Center for Cell Homeostasis, Ewha Womans University, Seoul 03760, Korea.
  • Min C; Department of Life Science, Ewha Womans University, Seoul 03760, Korea; Research Center for Cell Homeostasis, Ewha Womans University, Seoul 03760, Korea.
  • Lee DJ; Department of Life Science, Ewha Womans University, Seoul 03760, Korea; Research Center for Cell Homeostasis, Ewha Womans University, Seoul 03760, Korea.
  • Kang D; Department of Life Science, Ewha Womans University, Seoul 03760, Korea.
  • Song J; Department of Biochemistry, Yonsei University, Seoul 03722, Korea.
  • Kwon J; Department of Life Science, Ewha Womans University, Seoul 03760, Korea; Research Center for Cell Homeostasis, Ewha Womans University, Seoul 03760, Korea.
  • Kang SW; Department of Life Science, Ewha Womans University, Seoul 03760, Korea; Research Center for Cell Homeostasis, Ewha Womans University, Seoul 03760, Korea. Electronic address: kangsw@ewha.ac.kr.
Cell Rep ; 26(8): 2194-2211.e6, 2019 02 19.
Article in En | MEDLINE | ID: mdl-30784599
ABSTRACT
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-α-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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Apoptosis / Homeodomain Proteins Limits: Animals / Humans Language: En Journal: Cell Rep Year: 2019 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Apoptosis / Homeodomain Proteins Limits: Animals / Humans Language: En Journal: Cell Rep Year: 2019 Document type: Article