The mitochondrial pathway and reactive oxygen species are critical contributors to interferon-alpha/beta-mediated apoptosis in Ubp43-deficient hematopoietic cells

Abstract

UBP43 (also known as USP18) plays a role in the negative regulation of interferon-alpha/beta signaling, and bone marrow cells in Ubp43-deficient mice exhibited hypersensitivity to interferon-alpha/beta-mediated apoptosis. Here, we show that the mitochondrial apoptotic pathway and reactive oxygen species are major contributors to the elevated interferon-alpha/beta-mediated apoptosis in Ubp43-deficient mouse bone marrow cells and in UBP43-knockdown THP-1 cells. Furthermore, TRAIL and FASL, which were proposed as apoptosis inducers upon interferon-alpha/beta treatment in UBP43-knockdown adherent cancer cells, did not cause apoptosis in these hematopoietic cells. Therefore, although UBP43 depletion can cause hypersensitivity to interferon-alpha/beta-mediated apoptosis in a broad range of cell types, the downstream pathway may vary depending on the cell type. (C) 2012 Elsevier Inc. All rights reserved.