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bioRxiv · 10.1101/156901

Caspase-8, RIPK1, and RIPK3 Coordinately Regulate Retinoic Acid-Induced Cell Differentiation and Necroptosis

Someda, M.·Kuroki, S.·Tachibana, M.·Yonehara, S.
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Abstract

Caspase-8, which is essential for death receptor-mediated apoptosis, inhibits necroptosis by suppressing the function of RIPK1 and RIPK3 to activate MLKL. We show that knockdown of caspase-8 expression in embryoid bodies derived from ES cells markedly enhances retinoic acid (RA)-induced cell differentiation and necroptosis, both of which are dependent on Ripkl and Ripk3. RA treatment obviously enhanced the expression of RA-specific genes having a retinoic acid response element (RARE) to induce cell differentiation, and induced marked expression of RIPK1, RIPK3 and MLKL to stimulate necroptosis. Caspase-8 knockdown induced RA receptor (RAR) to form a complex with RIPK1 and RIPK3 in the nucleus, and RAR interacting with RIPK1 and RIPK3 showed much stronger binding activity to RARE than RAR without RIPK1 or RIPK3. In Caspase-8-deficient mouse embryos, expression of RA-specific genes was obviously enhanced. Thus, caspase-8, RIPK1, and RIPK3 regulate RA-induced cell differentiation and necroptosis both in vitro and in vivo.

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Someda, M., Kuroki, S., Tachibana, M., Yonehara, S.. 2017-06-28. Caspase-8, RIPK1, and RIPK3 Coordinately Regulate Retinoic Acid-Induced Cell Differentiation and Necroptosis. https://doi.org/10.1101/156901

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