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dc.contributor.authorBarbarulo, A-
dc.contributor.authorIansante, V-
dc.contributor.authorChaidos, A-
dc.contributor.authorNaresh, K-
dc.contributor.authorRahemtulla, A-
dc.contributor.authorFranzoso, G-
dc.contributor.authorKaradimitris, A-
dc.contributor.authorHaskard, DO-
dc.contributor.authorPapa, S-
dc.contributor.authorBubici, C-
dc.identifier.citationOncogene, 32(36), 4231 - 4242, 2013en_US
dc.descriptionCopyright @ 2013 Macmillan Publishers Limited. This is the author's accepted manuscript. The final published article is available from the link below.en_US
dc.description.abstractRegulation of cell survival is a key part of the pathogenesis of multiple myeloma (MM). Jun N-terminal kinase (JNK) signaling has been implicated in MM pathogenesis, but its function is unclear. To elucidate the role of JNK in MM, we evaluated the specific functions of the two major JNK proteins, JNK1 and JNK2. We show here that JNK2 is constitutively activated in a panel of MM cell lines and primary tumors. Using loss-of-function studies, we demonstrate that JNK2 is required for the survival of myeloma cells and constitutively suppresses JNK1-mediated apoptosis by affecting expression of poly(ADP-ribose) polymerase (PARP)14, a key regulator of B-cell survival. Strikingly, we found that PARP14 is highly expressed in myeloma plasma cells and associated with disease progression and poor survival. Overexpression of PARP14 completely rescued myeloma cells from apoptosis induced by JNK2 knockdown, indicating that PARP14 is critically involved in JNK2-dependent survival. Mechanistically, PARP14 was found to promote the survival of myeloma cells by binding and inhibiting JNK1. Moreover, inhibition of PARP14 enhances the sensitization of MM cells to anti-myeloma agents. Our findings reveal a novel regulatory pathway in myeloma cells through which JNK2 signals cell survival via PARP14, and identify PARP14 as a potential therapeutic target in myeloma.en_US
dc.description.sponsorshipKay Kendall Leukemia Fund, NIH, Cancer Research UK, Italian Association for Cancer Research and the Foundation for Liver Research.en_US
dc.publisherNature Publishing Groupen_US
dc.subjectC-Jun N-terminal kinaseen_US
dc.subjectMultiple myelomaen_US
dc.titlePoly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myelomaen_US
Appears in Collections:Biological Sciences
Dept of Life Sciences Research Papers

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