Imperial College London
Alternate

Dr Salvatore Papa

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Honorary Research Fellow
 
 
 
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Contact

 

+44 (0)20 3313 8282s.papa

 
 
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Location

 

10N.13Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Barbarulo:2013:10.1038/onc.2012.448,
author = {Barbarulo, A and Iansante, V and Chaidos, A and Naresh, K and Rahemtulla, A and Franzoso, G and Karadimitris, A and Haskard, DO and Papa, S and Bubici, C},
doi = {10.1038/onc.2012.448},
journal = {Oncogene},
pages = {4231--4242},
title = {Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma},
url = {http://dx.doi.org/10.1038/onc.2012.448},
volume = {32},
year = {2013}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Barbarulo,A
AU  - Iansante,V
AU  - Chaidos,A
AU  - Naresh,K
AU  - Rahemtulla,A
AU  - Franzoso,G
AU  - Karadimitris,A
AU  - Haskard,DO
AU  - Papa,S
AU  - Bubici,C
DO  - 10.1038/onc.2012.448
EP  - 4242
PY  - 2013///
SN  - 0950-9232
SP  - 4231
TI  - Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma
T2  - Oncogene
UR  - http://dx.doi.org/10.1038/onc.2012.448
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000324168000005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/onc2012448
VL  - 32
ER  -
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