PLAGL2 (Pleomorphic adenoma gene-like 2)

Identity

Other names	FLJ23283
	KIAA0198
Hugo	PLAGL2
Location	20q11.21

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
Hugo	PLAGL2
GDB	PLAGL2
Entrez_Gene	PLAGL2  5326  pleiomorphic adenoma gene-like 2
	Cards
Atlas	PLAGL2ID41738ch20q11
GeneCards	PLAGL2
Ensembl	PLAGL2 [Search_View]   ENSG00000126003 [Gene_View]
Genatlas	PLAGL2
GeneLynx	PLAGL2
eGenome	PLAGL2
euGene	5326
	Genomic and cartography
GoldenPath	PLAGL2  -  20q11.21   chr20:30243968-30259207 -  20q11.21   [Description]    (hg18-Mar_2006)
Ensembl	PLAGL2 - 20q11.21 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	PLAGL2
	Gene and transcription
Genbank	AF006005 [ ENTREZ ]
Genbank	AK026951 [ ENTREZ ]
Genbank	AK292450 [ ENTREZ ]
Genbank	BC023655 [ ENTREZ ]
Genbank	D83784 [ ENTREZ ]
RefSeq	NM_002657 [ SRS ]    NM_002657 [ ENTREZ ]
RefSeq	AC_000063 [ SRS ]    AC_000063 [ ENTREZ ]
RefSeq	NC_000020 [ SRS ]    NC_000020 [ ENTREZ ]
RefSeq	NT_028392 [ SRS ]    NT_028392 [ ENTREZ ]
RefSeq	NW_927339 [ SRS ]    NW_927339 [ ENTREZ ]
AceView	PLAGL2 AceView - NCBI
Unigene	Hs.154104 [ SRS ]    Hs.154104 [ NCBI ]     HS154104 [ spliceNest ]
Fast-db	7793 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q9UPG8 [ SRS]    Q9UPG8 [ EXPASY ]     Q9UPG8 [ INTERPRO ]
Prosite	PS00028 ZINC_FINGER_C2H2_1 [ SRS ]    PS00028 ZINC_FINGER_C2H2_1 [ Expasy ]
Prosite	PS50157 ZINC_FINGER_C2H2_2 [ SRS ]    PS50157 ZINC_FINGER_C2H2_2 [ Expasy ]
Interpro	IPR007087 Znf_C2H2 [ SRS ]    IPR007087 Znf_C2H2 [ EBI ]
Interpro	IPR015880 Znf_C2H2-like [ SRS ]    IPR015880 Znf_C2H2-like [ EBI ]
Interpro	IPR013087 Znf_C2H2/integrase_DNA-bd [ SRS ]    IPR013087 Znf_C2H2/integrase_DNA-bd [ EBI ]
CluSTr	Q9UPG8
Pfam	PF00096 zf-C2H2 [ SRS ]    PF00096 zf-C2H2 [ Sanger ]    pfam00096 [ NCBI-CDD ]
Smart	SM00355 ZnF_C2H2 [EMBL]
Blocks	Q9UPG8
HPRD	05333
	Protein Interaction databases
DIP	Q9UPG8
IntAct	Q9UPG8
	Polymorphism : SNP, mutations, diseases
OMIM	604866    [ map ]
GENECLINICS	604866
SNP	PLAGL2 [dbSNP-NCBI]
SNP	NM_002657 [SNP-NCI]
SNP	PLAGL2 [GeneSNPs - Utah]  PLAGL2] [HGBASE - SRS]
HAPMAP	PLAGL2 [HAPMAP]
COSMIC	PLAGL2 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	PLAGL2
	General knowledge
Family Browser	PLAGL2 [UCSC Family Browser]
SOURCE	NM_002657
SMD	Hs.154104
SAGE	Hs.154104
GO	transcription factor activity [Amigo]  transcription factor activity
GO	intracellular [Amigo]  intracellular
GO	nucleus [Amigo]  nucleus
GO	transcription [Amigo]  transcription
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	induction of apoptosis [Amigo]  induction of apoptosis
GO	zinc ion binding [Amigo]  zinc ion binding
GO	positive regulation of transcription from RNA polymerase II promoter [Amigo]  positive regulation of transcription from RNA polymerase II promoter
GO	metal ion binding [Amigo]  metal ion binding
PubGene	PLAGL2
TreeFam	PLAGL2
CTD	5326 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	PLAGL2 Related clones (RZPD - Berlin)
	PubMed
PubMed	11 Pubmed reference(s) in LocusLink

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

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Contributor(s)

Written	01-2008	Abbas 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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:26:02 2008