PMID- 11832486
OWN - NLM
STAT- MEDLINE
DCOM- 20020702
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 18
DP  - 2002 May 3
TI  - A zinc-finger protein, PLAGL2, induces the expression of a proapoptotic protein 
      Nip3, leading to cellular apoptosis.
PG  - 15851-8
AB  - Pleomorphic adenomas gene-like 2 (PLAGL2) protein containing seven C(2)H(2) zinc 
      finger motifs exhibits DNA binding and transcriptional activation activity and is 
      expressed in response to hypoxia or iron deficiency. To identify the target genes 
      of PLAGL2, we transfected mouse PLAGL2 cDNA into Balb/c3T3 fibroblasts and 
      neuroblastoma Neuro2a cells. Both cells were induced to undergo apoptosis by the 
      expression of PLAGL2 as judged by assays of TUNEL (terminal 
      deoxynucleotidyltransferase-mediated dUTP nick end-labeling), DNA fragmentation, 
      propidium iodide staining, and the binding of annexin V to the cell surface. The 
      treatment of the cells with an iron chelator, desferrioxamine, resulted in the 
      induction of apoptosis with a concomitant accumulation of PLAGL2 in the nucleus. 
      The expression of PLAGL2 in Balb/c3T3 cells led to the mRNA expression of a 
      proapoptotic factor, Nip3, which can dimerize with Bcl-2. Nip3 mRNA was also 
      induced in desferrioxamine-treated cells. Furthermore, the Nip3 promoter 
      containing a hypoxia-responsive element was activated by PLAGL2, independent of 
      hypoxia-inducible factor-1 (HIF-1). The transfection of antisense oligonucleotide 
      to mouse Nip3 mRNA into PLAGL2-expressing cells led to a decrease in apoptotic 
      cells compared with sense oligonucleotide-transfected cells. Despite the 
      activation of DNA-HIF-1 binding activity under hypoxic conditions, neither an 
      accumulation of HIF-1 alpha nor the activation of HIF-1 was observed following 
      the expression of PLAGL2. These results indicate that PLAGL2 is located 
      downstream of HIF-1 and suggest that PLAGL2 functions as a tumor suppressor in 
      association with HIF-1.
FAU - Mizutani, Atsushi
AU  - Mizutani A
AD  - Department of Biotechnology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 
      606-8585, Japan.
FAU - Furukawa, Takako
AU  - Furukawa T
FAU - Adachi, Yasushi
AU  - Adachi Y
FAU - Ikehara, Susumu
AU  - Ikehara S
FAU - Taketani, Shigeru
AU  - Taketani S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20020206
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Annexin A5)
RN  - 0 (BNIP3 protein, human)
RN  - 0 (BNIP3L protein, human)
RN  - 0 (DNA Probes)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oligodeoxyribonucleotides, Antisense)
RN  - 0 (Plagl2 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Thionucleotides)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - J06Y7MXW4D (Deferoxamine)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Annexin A5/metabolism
MH  - Apoptosis/drug effects/*physiology
MH  - Cell Hypoxia/physiology
MH  - Cell Membrane/metabolism
MH  - DNA Probes
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Deferoxamine/pharmacology
MH  - *Gene Expression Regulation
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - In Situ Nick-End Labeling
MH  - Membrane Proteins/*genetics
MH  - Mice
MH  - Neuroblastoma
MH  - Nuclear Proteins/metabolism
MH  - Oligodeoxyribonucleotides, Antisense/pharmacology
MH  - Promoter Regions, Genetic
MH  - *Proto-Oncogene Proteins
MH  - RNA-Binding Proteins/genetics/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Thionucleotides/pharmacology
MH  - Trans-Activators/metabolism
MH  - Transcription Factors/metabolism
MH  - Transcription, Genetic
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - *Tumor Suppressor Proteins
MH  - Zinc Fingers
EDAT- 2002/02/08 10:00
MHDA- 2002/07/03 10:01
CRDT- 2002/02/08 10:00
PHST- 2002/02/08 10:00 [pubmed]
PHST- 2002/07/03 10:01 [medline]
PHST- 2002/02/08 10:00 [entrez]
AID - S0021-9258(19)35738-2 [pii]
AID - 10.1074/jbc.M111431200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 May 3;277(18):15851-8. doi: 10.1074/jbc.M111431200. Epub 2002 
      Feb 6.