PMID- 21087599
OWN - NLM
STAT- MEDLINE
DCOM- 20110223
LR  - 20171213
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 81
IP  - 4
DP  - 2011 Feb 15
TI  - ABC50 modulates sensitivity of HL60 leukemic cells to endoplasmic reticulum (ER) 
      stress-induced cell death.
PG  - 488-97
LID - 10.1016/j.bcp.2010.11.007 [doi]
AB  - ABC50 (aka ABCF1) is a member of the ATP Binding Cassette protein family. ABC50 
      stimulates complex formation between eIF2, GTP and Met-tRNA implicating it in 
      translation initiation. Econazole (Ec) is an imidazole anti-fungal that induces 
      endoplasmic reticulum (ER) stress in mammalian cells by promoting ER Ca(2+) 
      depletion and sustained protein synthesis inhibition. HL60 cells selected for Ec 
      resistance were found to exhibit a multi-drug resistance phenotype associated 
      specifically with ER stress. Differential Display was used to identify ABC50 as 
      an overexpressed gene in resistant cells. ABC50 knockdown (KD) in Ec-resistant 
      HL60 cells partially restored Ec sensitivity. In parental HL60 cells, ABC50 KD 
      increased sensitivity to Ec, thapsigargin and tunicamycin but not to serum 
      withdrawal or etoposide. ABC50 overexpression (OE) partially and specifically 
      decreased sensitivity to ER stress agents. ABC50 KD or OE had no effect on ROS 
      generation by Ec, ER Ca(2+) stores or thapsigargin-stimulated influx. Increased 
      eIF2alpha phosphorylation in response to ER stress was observed in the KD cells while 
      decreased phosphorylation was observed in the OE cells. Ribosomal content was 
      reduced in ABC50 KD cells and increased in OE cells. Knockdown suppressed protein 
      synthesis while OE increased it. Protein synthesis was sustained in ABC50 OE 
      cells exposed to Ec. ABC50 OE promoted ER stress resistance and increased 
      antibody production in the hybridoma GK1.5 suggesting it may be useful for the 
      overproduction of specific proteins. Taken together, these results indicate that 
      ABC50 modulates sensitivity to Ec and other ER stress agents primarily through 
      its effects on protein synthesis.
CI  - Copyright A(c) 2010 Elsevier Inc. All rights reserved.
FAU - Yu, Yongmao
AU  - Yu Y
AD  - Arthritis and Immune Disorder Research Centre, TGRI, University Health Network, 
      Canada.
FAU - Zhang, Yicheng
AU  - Zhang Y
FAU - Zhu, Ziping
AU  - Zhu Z
FAU - Berger, Stuart A
AU  - Berger SA
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101116
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (ABCF1 protein, human)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 11089-65-9 (Tunicamycin)
RN  - 67526-95-8 (Thapsigargin)
RN  - 6Z1Y2V4A7M (Econazole)
SB  - IM
MH  - ATP-Binding Cassette Transporters/*physiology
MH  - *Cell Death
MH  - Drug Resistance, Multiple
MH  - Econazole/pharmacology
MH  - Endoplasmic Reticulum/*physiology
MH  - HL-60 Cells
MH  - Humans
MH  - *Protein Biosynthesis
MH  - Stress, Physiological
MH  - Thapsigargin/pharmacology
MH  - Tunicamycin/pharmacology
EDAT- 2010/11/23 06:00
MHDA- 2011/02/24 06:00
CRDT- 2010/11/20 06:00
PHST- 2010/09/02 00:00 [received]
PHST- 2010/11/08 00:00 [revised]
PHST- 2010/11/08 00:00 [accepted]
PHST- 2010/11/20 06:00 [entrez]
PHST- 2010/11/23 06:00 [pubmed]
PHST- 2011/02/24 06:00 [medline]
AID - S0006-2952(10)00804-X [pii]
AID - 10.1016/j.bcp.2010.11.007 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2011 Feb 15;81(4):488-97. doi: 10.1016/j.bcp.2010.11.007. Epub 
      2010 Nov 16.