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Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma.
MedLine Citation:
PMID:  23045269     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Regulation 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.Oncogene advance online publication, 8 October 2012; doi:10.1038/onc.2012.448.
Authors:
A Barbarulo; V Iansante; A Chaidos; K Naresh; A Rahemtulla; G Franzoso; A Karadimitris; D O Haskard; S Papa; C Bubici
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-08
Journal Detail:
Title:  Oncogene     Volume:  -     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Section of Inflammation and Signal Transduction, Department of Medicine, Imperial College, London, UK.
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