PLAGL2 (Pleomorphic adenoma gene-like 2)

2008-01-01   Abbas Abdollahi  

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

Identity

HGNC
LOCATION
20q11.21
LOCUSID
ALIAS
ZNF900

DNA/RNA

Atlas Image
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.

Proteins

Atlas Image

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 name
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.

Article Bibliography

Pubmed IDLast YearTitleAuthors
170634612007LOT1 (ZAC1/PLAGL1) and its family members: mechanisms and functions.Abdollahi A et al
91503641997Identification of a zinc-finger gene at 6q25: a chromosomal region implicated in development of many solid tumors.Abdollahi A et al
174629952007Binding 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 et al
150446902004Identification of genes that synergize with Cbfb-MYH11 in the pathogenesis of acute myeloid leukemia.Castilla LH et al
114987942001Involvement of PLAGL2 in activation of iron deficient- and hypoxia-induced gene expression in mouse cell lines.Furukawa T et al
176186022007PLAGL2 translocation and SP-C promoter activity--a cellular response of lung cells to hypoxia.Guo Y et al
118889282002The tumorigenic diversity of the three PLAG family members is associated with different DNA binding capacities.Hensen K et al
97225271998Transcriptional activation capacity of the novel PLAG family of zinc finger proteins.Kas K et al
164134722006Cbf beta-SMMHC induces distinct abnormal myeloid progenitors able to develop acute myeloid leukemia.Kuo YH et al
155856522005Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11.Landrette SF et al
118324862002A zinc-finger protein, PLAGL2, induces the expression of a proapoptotic protein Nip3, leading to cellular apoptosis.Mizutani A et al
175519692008Tip60 modulates PLAGL2-mediated transactivation by acetylation.Ning J et al
163787572006Cloning and embryonic expression of zebrafish PLAG genes.Pendeville H et al
91842261997Regulation of apoptosis and cell cycle arrest by Zac1, a novel zinc finger protein expressed in the pituitary gland and the brain.Spengler D et al
173329142007PLAG1, the prototype of the PLAG gene family: versatility in tumour development (review).Van Dyck F et al
106468612000PLAG1, the main translocation target in pleomorphic adenoma of the salivary glands, is a positive regulator of IGF-II.Voz ML et al
153613642005Pleiomorphic adenoma gene-like-2, a zinc finger protein, transactivates the surfactant protein-C promoter.Yang MC et al
179502442007PLAGL2 controls the stability of Pirh2, an E3 ubiquitin ligase for p53.Zheng G et al
162077152005Sumoylation and acetylation play opposite roles in the transactivation of PLAG1 and PLAGL2.Zheng G et al

Other Information

Locus ID:

NCBI: 5326
MIM: 604866
HGNC: 9047
Ensembl: ENSG00000126003

Variants:

dbSNP: 5326
ClinVar: 5326
TCGA: ENSG00000126003
COSMIC: PLAGL2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000126003ENST00000246229Q9UPG8

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
385003862024POFUT1 and PLAGL2 are characteristic markers of mucinous colorectal cancer associated with MUC2 expression.0
385003862024POFUT1 and PLAGL2 are characteristic markers of mucinous colorectal cancer associated with MUC2 expression.0
363993092023PLAGL2 increases adriamycin resistance and EMT in breast cancer cells by activating the Wnt pathway.3
364374152023Amplification of the PLAG-family genes-PLAGL1 and PLAGL2-is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification.8
366209072023PLAGL2 promotes the stemness and is upregulated by transcription factor E2F1 in human lung cancer.2
368074692023Long non-coding RNA LGALS8-AS1 facilitates PLAGL2-mediated malignant phenotypes in gastric cancer.0
369998032023PLAGL2 promotes Snail expression and gastric cancer progression via UCA1/miR-145-5p/YTHDF1 axis.7
363993092023PLAGL2 increases adriamycin resistance and EMT in breast cancer cells by activating the Wnt pathway.3
364374152023Amplification of the PLAG-family genes-PLAGL1 and PLAGL2-is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification.8
366209072023PLAGL2 promotes the stemness and is upregulated by transcription factor E2F1 in human lung cancer.2
368074692023Long non-coding RNA LGALS8-AS1 facilitates PLAGL2-mediated malignant phenotypes in gastric cancer.0
369998032023PLAGL2 promotes Snail expression and gastric cancer progression via UCA1/miR-145-5p/YTHDF1 axis.7
343316122022LncRNA HCP5 acts as a miR-128-3p sponge to promote the progression of multiple myeloma through activating Wnt/β-catenin/cyclin D1 signaling via PLAGL2.12
357777952022PLAGL2 Promotes the Proliferation and Migration of Diffuse Large B-cell Lymphoma Cells via Wnt/β-catenin Pathway.1
343316122022LncRNA HCP5 acts as a miR-128-3p sponge to promote the progression of multiple myeloma through activating Wnt/β-catenin/cyclin D1 signaling via PLAGL2.12

Citation

Abbas Abdollahi

PLAGL2 (Pleomorphic adenoma gene-like 2)

Atlas Genet Cytogenet Oncol Haematol. 2008-01-01

Online version: http://atlasgeneticsoncology.org/gene/41738/plagl2-(pleomorphic-adenoma-gene-like-2)