PMID- 18041764
OWN - NLM
STAT- MEDLINE
DCOM- 20080501
LR  - 20211203
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 103
IP  - 2
DP  - 2008 Feb 1
TI  - Overexpression of Par-4 enhances thapsigargin-induced apoptosis via 
      down-regulation of XIAP and inactivation of Akt in human renal cancer cells.
PG  - 358-68
AB  - The prostate-apoptosis-response-gene-4 (Par-4) protein has been shown to function 
      as an effector of cell death in response to various apoptotic stimuli that 
      trigger mitochondria and membrane receptor-mediated cell death pathways. We found 
      that overexpressing Par-4 by stable transfection sensitizes Caki cells to 
      induction of apoptosis by TRAIL and drugs that induce endoplasmic reticulum (ER) 
      stress [thapsigargin (TG), tunicamycin (TU) and etoposide]. Ectopic expression of 
      Par-4 is associated with decreased levels of XIAP protein in TG-treated cells, 
      caused in part by XIAP protein instability and caspase activation. Levels of 
      phospho-Akt are decreased in Caki/Par-4 cells to a significantly greater extent 
      than in Caki/Vector cells by treatment with TG, and this is in turn associated 
      with decreased levels of phospho-PDK1, the kinase upstream of Akt. In conclusion, 
      we provide evidence that ectopic expression of Par-4 sensitizes Caki cells to TG 
      and that XIAP protein instability and inactivation of Akt are important in 
      cellular pathways affected by Par-4.
CI  - (c) 2007 Wiley-Liss, Inc.
FAU - Lee, Tae-Jin
AU  - Lee TJ
AD  - Department of Immunology and Chronic Disease Research Center and Institute for 
      Medical Science, School of Medicine, Keimyung University, 194 DongSan-Dong 
      Jung-Gu, Taegu 700-712, South Korea.
FAU - Lee, Jung-Tae
AU  - Lee JT
FAU - Kim, Sang Hyun
AU  - Kim SH
FAU - Choi, Yung Hyun
AU  - Choi YH
FAU - Song, Kyoung Seob
AU  - Song KS
FAU - Park, Jong-Wook
AU  - Park JW
FAU - Kwon, Taeg Kyu
AU  - Kwon TK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (PDK1 protein, human)
RN  - 0 (Pyruvate Dehydrogenase Acetyl-Transferring Kinase)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (X-Linked Inhibitor of Apoptosis Protein)
RN  - 0 (XIAP protein, human)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
RN  - 0 (prostate apoptosis response-4 protein)
RN  - 67526-95-8 (Thapsigargin)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Adenocarcinoma, Clear Cell/*pathology
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins/genetics/*physiology
MH  - Caspases/metabolism
MH  - Cell Division/drug effects
MH  - Cell Line, Tumor/drug effects
MH  - Endoplasmic Reticulum/metabolism
MH  - Enzyme Activation/drug effects
MH  - Etoposide/pharmacology
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Kidney Neoplasms/*pathology
MH  - Phosphorylation/drug effects
MH  - Protein Processing, Post-Translational/drug effects
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors
MH  - Pyruvate Dehydrogenase Acetyl-Transferring Kinase
MH  - Recombinant Fusion Proteins/physiology
MH  - TNF-Related Apoptosis-Inducing Ligand/pharmacology
MH  - Thapsigargin/*pharmacology
MH  - Transfection
MH  - X-Linked Inhibitor of Apoptosis Protein/genetics/metabolism
EDAT- 2007/11/29 09:00
MHDA- 2008/05/02 09:00
CRDT- 2007/11/29 09:00
PHST- 2007/11/29 09:00 [pubmed]
PHST- 2008/05/02 09:00 [medline]
PHST- 2007/11/29 09:00 [entrez]
AID - 10.1002/jcb.21642 [doi]
PST - ppublish
SO  - J Cell Biochem. 2008 Feb 1;103(2):358-68. doi: 10.1002/jcb.21642.