Absence of Cytosolic 2-Cys Prx Subtypes I and II Exacerbates TNF-α-Induced Apoptosis via Different Routes

Sunmi Lee, Joo Young Lee, Eun Woo Lee, Sujin Park, Dong Hoon Kang, Chengchun Min, Doo Jae Lee, Dongmin Kang, Jaewhan Song, Jongbum Kwon, Sang Won Kang

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3 Citations (Scopus)

Abstract

There are abundant peroxiredoxin (Prx) enzymes, but an increase of cellular H 2 O 2 level always happens in apoptotic cells. Here, we show that cellular H 2 O 2 switches different apoptosis pathways depending on which type of Prx enzyme is absent. TNF-α-induced H 2 O 2 burst preferentially activates the DNA damage-dependent apoptosis pathway in the absence of PrxI. By contrast, the same H 2 O 2 burst stimulates the RIPK1-dependent apoptosis pathway in the absence of PrxII by inducing the destruction of cIAP1 in caveolar membrane. Specifically, H 2 O 2 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.

Original languageEnglish
Pages (from-to)2194-2211.e6
JournalCell Reports
Volume26
Issue number8
DOIs
Publication statusPublished - 2019 Feb 19

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Lee, S., Lee, J. Y., Lee, E. W., Park, S., Kang, D. H., Min, C., Lee, D. J., Kang, D., Song, J., Kwon, J., & Kang, S. W. (2019). Absence of Cytosolic 2-Cys Prx Subtypes I and II Exacerbates TNF-α-Induced Apoptosis via Different Routes. Cell Reports, 26(8), 2194-2211.e6. https://doi.org/10.1016/j.celrep.2019.01.081