PMID- 19352384
OWN - NLM
STAT- MEDLINE
DCOM- 20090514
LR  - 20211020
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 100
IP  - 9
DP  - 2009 May 5
TI  - Differential activation of JNK1 isoforms by TRAIL receptors modulate apoptosis of 
      colon cancer cell lines.
PG  - 1415-24
LID - 10.1038/sj.bjc.6605021 [doi]
AB  - Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces 
      apoptosis on binding to its receptors, death receptor 4 and 5 (DR4, DR5). TRAIL 
      can also activate c-Jun N-terminal kinase (JNK) through the adaptor molecules, 
      TNF receptor-associated factor 2 (TRAF2) and receptor-interacting protein (RIP). 
      The role of JNK in TRAIL-induced tumour cell apoptosis is unclear. In this study, 
      we demonstrate that JNK is activated by TRAIL in colon cancer cells. Inhibition 
      of JNK with L-JNKI reduced rhTRAIL-induced cell death but enhanced cell death 
      induced by selective activation of DR4 or DR5. This difference was unrelated to 
      receptor internalisation or differential activation of c-Jun, but activation of 
      different JNK isoforms. Our data demonstrate that JNK1, but not JNK2 is activated 
      by rhTRAIL in the examined colon cancer cell lines. Although rhTRAIL activated 
      both the long and short isoforms of JNK1, selective activation of DR4 or DR5 led 
      to predominant activation of the short JNK1 isoforms (JNK1alpha1 and/or 
      JNK1beta1). Knockdown of JNK1alpha1 by shRNA enhanced apoptosis induced by TRAIL, 
      agonistic DR4 or DR5 antibodies. On the other hand, knockdown of the long JNK1 
      isoforms (JNK1alpha2 and JNK1beta2) had the opposite effect; it reduced 
      TRAIL-induced cell death. These data indicate that the short JNK1 isoforms 
      transmit an antiapoptotic signal, whereas the long isoforms (JNK1alpha2 or 
      JNK1beta2) act in a proapoptotic manner.
FAU - Mahalingam, D
AU  - Mahalingam D
AD  - Cell Stress and Apoptosis Research Group, Department of Biochemistry and National 
      Centre of Biomedical Engineering Science, National University of Ireland, 
      University Road, Galway, Ireland.
FAU - Keane, M
AU  - Keane M
FAU - Pirianov, G
AU  - Pirianov G
FAU - Mehmet, H
AU  - Mehmet H
FAU - Samali, A
AU  - Samali A
FAU - Szegezdi, E
AU  - Szegezdi E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090407
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (DNA Primers)
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Cell Death/drug effects
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/enzymology/genetics/*metabolism/pathology
MH  - DNA Primers
MH  - Enzyme Activation/drug effects
MH  - Flow Cytometry
MH  - Humans
MH  - Isoenzymes/drug effects/metabolism
MH  - Kinetics
MH  - Mitogen-Activated Protein Kinase 8/drug effects/genetics/*metabolism
MH  - Plasmids
MH  - RNA, Neoplasm/genetics/isolation & purification
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/*metabolism/*therapeutic use
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transfection
PMC - PMC2694422
EDAT- 2009/04/09 09:00
MHDA- 2009/05/15 09:00
PMCR- 2010/05/05
CRDT- 2009/04/09 09:00
PHST- 2009/04/09 09:00 [entrez]
PHST- 2009/04/09 09:00 [pubmed]
PHST- 2009/05/15 09:00 [medline]
PHST- 2010/05/05 00:00 [pmc-release]
AID - 6605021 [pii]
AID - 10.1038/sj.bjc.6605021 [doi]
PST - ppublish
SO  - Br J Cancer. 2009 May 5;100(9):1415-24. doi: 10.1038/sj.bjc.6605021. Epub 2009 
      Apr 7.