The mitochondrial pathway and reactive oxygen species are critical contributors to interferon-α/β-mediated apoptosis in Ubp43-deficient hematopoietic cells.
UBP43 (also known as USP18) plays a role in the negative regulation of interferon-α/β signaling, and bone marrow cells in Ubp43-deficient mice exhibited hypersensitivity to interferon-α/β-mediated apoptosis. Here, we show that the mitochondrial apoptotic pathway and reactive oxygen species are major contributors to the elevated interferon-α/β-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-α/β treatment in UBP43-knockdown adherent cancer cells, did not cause apoptosis in these hematopoietic cells. Therefore, although UBP43 depletion can cause hypersensitivity to interferon-α/β-mediated apoptosis in a broad range of cell types, the downstream pathway may vary depending on the cell type.
Department of Biological Sciences, Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, South Korea.
Hwa Young
HY
Yim
Young
Y
Yang
Jong-Seok
JS
Lim
Myeong Seok
MS
Lee
Dong-Er
DE
Zhang
Keun Il
KI
Kim
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology* / Q000494:pharmacology; D016899:Interferon-beta / Q000276:immunology* / Q000494:pharmacology; D053858:Metabolic Networks and Pathways; D051379:Mice; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D043222:Ubiquitin Thiolesterase
D053222:Fas Ligand Protein; D016898:Interferon-alpha; D017382:Reactive Oxygen Species; D053221:TNF-Related Apoptosis-Inducing Ligand; D016899:Interferon-beta; D010450:Endopeptidases; C118306:Usp18 protein, mouse; C485560:USP18 protein, human; D043222:Ubiquitin Thiolesterase; D053148:Caspase 3