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PLAGL2 (Pleomorphic adenoma gene-like 2)

Identity

Other namesFLJ23283
KIAA0198
HGNC (Hugo) PLAGL2
Location 20q11.21
Location_base_pair Starts at 30243968 and ends at 30259207 bp from pter ( according to hg18-Mar_2006)  [Mapping]

DNA/RNA

 
  PLAGL2 exons and corresponding nucleotide numbers on each GenBank sequence database are shown in this table.
Description PLAGL2 (PLAG-Like 2; a PLAG family member; GenBank accession number AF006005) was identified by homology searches of the database of expressed sequence tags (ESTs) and sequence similarity to zinc-finger region of the human PLAGL1/LOT1/ZAC1 and PLAG1 proteins.

Protein

 
Description PLAGL2 protein consists of 496 amino acid residues, six C2H2-type zinc finger domains in its amino-terminal region (shown as brown in the figure), and a proline- and serine-rich carboxyl terminus (shown as blue).
Expression Northern analysis showed that the PLAGL2 mRNA is expressed in fetal kidney, liver, lung, and brain but not in adult tissues. However, PCR analysis showed that PLAGL2 is ubiquitously expressed in almost all adult and fetal human tissues, except for the relatively low level of expression observed in fetal brain.
Localisation Nuclear.
Function PLAGL2 can bind and activate human insulin-like growth factor II (IGF II) gene promoter; therefore, the oncogenic capacity of PLAGL2 may be mediated by activating the IGF-II mitogenic pathway. However, PLAGL2, possibly by association with HIF-1, may also have apoptotic role since it can activate Nip3 promoter and induce transcription in Balb/c3T3 fibroblasts and Neuro2a neuroblastoma cells, leading to apoptosis. PLAGL2 mRNA can be induced upon iron deficiency or hypoxia in mouse macrophage cell line RAW264.7, mouse erythroleukemia (MEL) cells, and Balb/c3T3 cells. In addition, PLAGL2 can also transactivate the surfactant protein-C (SP-C), a protein whose expression occurs principally in type II pneumocytes located in the distal lung alveolae. Additional data suggest that repression of the transactivating capacity of PLAGL2 may be directly related to sumoylation. Also, PLAGL2 protein is acetylated and activated by p300 and deacetylated and repressed by HDAC7, involving the lysine residues as the acetylation target. Therefore, it appears that the activity of PLAGL2 is tightly modulated by both sumoylation and acetylation, which may have opposite effects on their transactivation. Tip60 can modulate PLAGL2 function through both acetylation and inhibition of sumoylation, resulting in an enhanced PLAGL2-mediated transactivation. PLAGL2 can bind and stabilize (by preventing proteasomal degradation) Pirh2 dimer, a p53 inducible E3 ligase involved in the ubiquitination of p53. PLAGL2 can also regulate NCF2 gene expression through binding to the tumor necrosis factor (TNF)-alpha-responsive region of the NCF2 promoter, thus regulating p67(phox) expression and NADPH oxidase activity. PLAGL2 was recently found to aid in the efficient uptake of chylomicrons by intestinal lacteal vessels.
Homology Homologous to the human PLAG1 and PLAGL1 proteins.

Mutations

Note Mutation has not been reported in the PLAGL2 coding region.

Implicated in

Entity Carcinogenicity
Note PLAGL2 is an oncoprotein involved in various malignancies including lipoblastomas, hepatoblastomas, and acute myeloid leukemia. PLAGL2 expression is increased in human cancers including acute myeloid leukemia (AML). The expression is increased in 20% of human AML samples. The PLAGL2 gene can independently cooperate with CBFB- MYH11 fusion gene in leukemogenesis. AML subtype M4 with eosinophilia is associated with a chromosome 16 inversion that creates a fusion gene CBFB-MYH11, encoding CBFbeta-SMMHC fusion protein. This fusion protein inhibits the core-binding factor (CBF), resulting in a block of hematopoietic differentiation and induction of leukemia in the presence of additional mutations.
Disease Cancer; lipoblastomas, hepatoblastomas, and acute myeloid leukemia.
  

External links

Nomenclature
HGNC (Hugo)PLAGL2   9047
Entrez_Gene (NCBI)PLAGL2  5326  pleiomorphic adenoma gene-like 2
Cards
AtlasPLAGL2ID41738ch20q11
GeneCards (Weizmann)PLAGL2
Ensembl (Hinxton)ENSG00000126003 [Gene_View]  PLAGL2 [Vega]
AceView (NCBI)PLAGL2
Genatlas (Paris)PLAGL2
euGene (Indiana)5326
SOURCE (Stanford)NM_002657
Genomic and cartography
GoldenPath (UCSC)PLAGL2  -  20q11.21   chr20:30243968-30259207 -  20q11.21   [Description]    (hg18-Mar_2006)
EnsemblPLAGL2 - 20q11.21 [CytoView]
Mapping of homologs : NCBIPLAGL2 [Mapview]
OMIM604866   
Gene and transcription
Gene : Genbank (Entrez)AF006005 AK026951 AK292450 BC023655 D83784
Reference sequence (RefSeq transcript) :SRSNM_002657
Reference transcript : EntrezNM_002657
RefSeq genomic : SRSAC_000063 AC_000152 NC_000020 NT_028392 NW_001838664 NW_927339
RefSeq genomic : EntrezAC_000063 AC_000152 NC_000020 NT_028392 NW_001838664 NW_927339
Consensus coding sequences : CCDS NCBIPLAGL2
Cluster EST : UnigeneHs.154104 [ SRS ] Hs.154104 [ NCBI ]
Alternative Splicing : Fast-db (Paris)7793
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtQ9UPG8 (SRS) Q9UPG8 (Expasy) Q9UPG8 (Uniprot)
With graphics : InterProQ9UPG8
Splice isoforms : VarSplice FASTAQ9UPG8(VarSplice FASTA)
Domaine pattern : Prosite (SRS)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domain pattern : Prosite (Expaxy)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domains : Interpro (SRS)Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
Domains : Interpro (EBI)Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
Related proteins : CluSTrQ9UPG8
Domain families : Pfam SRSzf-C2H2 (PF00096)   
Domain families : Pfam Sangerzf-C2H2 (PF00096)   
Domain families : Pfam NCBIpfam00096   
Domain families : Smart EMBLZnF_C2H2 (SM00355)
Blocks (Seattle)Q9UPG8
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
HPRD05333
Protein Interaction databases
DIP (DOE-UCLA)Q9UPG8
IntAct (EBI)Q9UPG8
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIPLAGL2
SNP : GeneSNP UtahPLAGL2
SNP : HGBasePLAGL2
Genetic variants : HAPMAPPLAGL2
Somatic Mutations in Cancer : COSMICPLAGL2 
Mutations and Diseases : HGMDPLAGL2
Hereditary diseases : OMIM604866   
Hereditary diseases : GENETests604866   
Diseases : Genetic AssociationPLAGL2
General knowledge
Homologs : HomoloGenePLAGL2
Homology/Alignments : Family Browser UCSCPLAGL2
Phylogenetic Trees/Animal Genes : TreeFamPLAGL2
Chemical/Protein Interactions : CTD5326
Keywords Ontology : AmiGOtranscription factor activity  intracellular  nucleus  cytoplasm  transcription  regulation of transcription, DNA-dependent  induction of apoptosis  zinc ion binding  positive regulation of transcription from RNA polymerase II promoter  metal ion binding  
Keywords Ontology : EGO-EBItranscription factor activity  intracellular  nucleus  cytoplasm  transcription  regulation of transcription, DNA-dependent  induction of apoptosis  zinc ion binding  positive regulation of transcription from RNA polymerase II promoter  metal ion binding  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Probes
Probes : ImagenesPLAGL2 Related clones (RZPD - Berlin)
Literature
PubMed14 Pubmed reference(s) in Entrez
PubGenePLAGL2

Bibliography

Identification of a gene containing zinc-finger motifs based on lost expression in malignantly transformed rat ovarian surface epithelial cells.
Abdollahi A, Godwin AK, Miller PD, Getts LA, Schultz DC, Taguchi T, Testa JR, Hamilton TC
Cancer research. 1997 ; 57 (10) : 2029-2034.
PMID 9158001
 
Identification of a zinc-finger gene at 6q25: a chromosomal region implicated in development of many solid tumors.
Abdollahi A, Roberts D, Godwin AK, Schultz DC, Sonoda G, Testa JR, Hamilton TC
Oncogene. 1997 ; 14 (16) : 1973-1979.
PMID 9150364
 
Regulation of apoptosis and cell cycle arrest by Zac1, a novel zinc finger protein expressed in the pituitary gland and the brain.
Spengler D, Villalba M, Hoffmann A, Pantaloni C, Houssami S, Bockaert J, Journot L
The EMBO journal. 1997 ; 16 (10) : 2814-2825.
PMID 9184226
 
Transcriptional activation capacity of the novel PLAG family of zinc finger proteins.
Kas K, Voz ML, Hensen K, Meyen E, Van de Ven WJ
The Journal of biological chemistry. 1998 ; 273 (36) : 23026-23032.
PMID 9722527
 
PLAG1, the main translocation target in pleomorphic adenoma of the salivary glands, is a positive regulator of IGF-II.
Voz ML, Agten NS, Van de Ven WJ, Kas K
Cancer research. 2000 ; 60 (1) : 106-113.
PMID 10646861
 
Involvement of PLAGL2 in activation of iron deficient- and hypoxia-induced gene expression in mouse cell lines.
Furukawa T, Adachi Y, Fujisawa J, Kambe T, Yamaguchi-Iwai Y, Sasaki R, Kuwahara J, Ikehara S, Tokunaga R, Taketani S
Oncogene. 2001 ; 20 (34) : 4718-4727.
PMID 11498794
 
The tumorigenic diversity of the three PLAG family members is associated with different DNA binding capacities.
Hensen K, Van Valckenborgh IC, Kas K, Van de Ven WJ, Voz ML
Cancer research. 2002 ; 62 (5) : 1510-1517.
PMID 11888928
 
A zinc-finger protein, PLAGL2, induces the expression of a proapoptotic protein Nip3, leading to cellular apoptosis.
Mizutani A, Furukawa T, Adachi Y, Ikehara S, Taketani S
The Journal of biological chemistry. 2002 ; 277 (18) : 15851-15858.
PMID 11832486
 
Identification of genes that synergize with Cbfb-MYH11 in the pathogenesis of acute myeloid leukemia.
Castilla LH, Perrat P, Martinez NJ, Landrette SF, Keys R, Oikemus S, Flanegan J, Heilman S, Garrett L, Dutra A, Anderson S, Pihan GA, Wolff L, Liu PP
Proceedings of the National Academy of Sciences of the United States of America. 2004 ; 101 (14) : 4924-4929.
PMID 15044690
 
Repression of the Transactivating Capacity of the Oncoprotein PLAG1 by SUMOylation.
Van Dyck F, Delvaux EL, Van de Ven WJ, Chavez MV
The Journal of biological chemistry. 2004 ; 279 (34) : 36121-36131.
PMID 15208321
 
Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11.
Landrette SF, Kuo YH, Hensen K, Barjesteh van Waalwijk van Doorn-Khosrovani S, Perrat PN, Van de Ven WJ, Delwel R, Castilla LH
Blood. 2005 ; 105 (7) : 2900-2907.
PMID 15585652
 
Pleiomorphic adenoma gene-like-2, a zinc finger protein, transactivates the surfactant protein-C promoter.
Yang MC, Weissler JC, Terada LS, Deng F, Yang YS
American journal of respiratory cell and molecular biology. 2005 ; 32 (1) : 35-43.
PMID 15361364
 
Sumoylation and acetylation play opposite roles in the transactivation of PLAG1 and PLAGL2.
Zheng G, Yang YC
The Journal of biological chemistry. 2005 ; 280 (49) : 40773-40781.
PMID 16207715
 
Cbf beta-SMMHC induces distinct abnormal myeloid progenitors able to develop acute myeloid leukemia.
Kuo YH, Landrette SF, Heilman SA, Perrat PN, Garrett L, Liu PP, Le Beau MM, Kogan SC, Castilla LH
Cancer cell. 2006 ; 9 (1) : 57-68.
PMID 16413472
 
Cloning and embryonic expression of zebrafish PLAG genes.
Pendeville H, Peers B, Kas K, Voz ML
Gene expression patterns : GEP. 2006 ; 6 (3) : 267-276.
PMID 16378757
 
LOT1 (ZAC1/PLAGL1) and its family members: mechanisms and functions.
Abdollahi A
Journal of cellular physiology. 2007 ; 210 (1) : 16-25.
PMID 17063461
 
Binding of pleomorphic adenoma gene-like 2 to the tumor necrosis factor (TNF)-alpha-responsive region of the NCF2 promoter regulates p67(phox) expression and NADPH oxidase activity.
Ammons MC, Siemsen DW, Nelson-Overton LK, Quinn MT, Gauss KA
The Journal of biological chemistry. 2007 ; 282 (24) : 17941-17952.
PMID 17462995
 
PLAGL2 translocation and SP-C promoter activity--a cellular response of lung cells to hypoxia.
Guo Y, Yang MC, Weissler JC, Yang YS
Biochemical and biophysical research communications. 2007 ; 360 (3) : 659-665.
PMID 17618602
 
Tip60 modulates PLAGL2-mediated transactivation by acetylation.
Ning J, Zheng G, Yang YC
Journal of cellular biochemistry. 2008 ; 103 (3) : 730-739.
PMID 17551969
 
Loss of the PlagL2 transcription factor affects lacteal uptake of chylomicrons.
Van Dyck F, Braem CV, Chen Z, Declercq J, Deckers R, Kim BM, Ito S, Wu MK, Cohen DE, Dewerchin M, Derua R, Waelkens E, Fiette L, Roebroek A, Schuit F, Van de Ven WJ, Shivdasani RA
Cell metabolism. 2007 ; 6 (5) : 406-413.
PMID 17983586
 
PLAG1, the prototype of the PLAG gene family: versatility in tumour development (review).
Van Dyck F, Declercq J, Braem CV, Van de Ven WJ
International journal of oncology. 2007 ; 30 (4) : 765-774.
PMID 17332914
 
PLAGL2 controls the stability of Pirh2, an E3 ubiquitin ligase for p53.
Zheng G, Ning J, Yang YC
Biochemical and biophysical research communications. 2007 ; 364 (2) : 344-350.
PMID 17950244
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written01-2008Abbas Abdollahi
Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, BioLife Sciences Building, Suite 446, Temple University, 1900 North 12th Street, Philadelphia, PA 19122, USA

Citation

This paper should be referenced as such :
Abdollahi A . PLAGL2 (Pleomorphic adenoma gene-like 2). Atlas Genet Cytogenet Oncol Haematol. January 2008 .
URL : http://AtlasGeneticsOncology.org/Genes/PLAGL2ID41738ch20q11.html

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indexed on : Sat Jun 27 16:42:08 CEST 2009

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