Written | 2008-01 | 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 |
Alias_names | pleiomorphic adenoma gene-like 2 |
Alias_symbol (synonym) | ZNF900 |
Other alias | FLJ23283 |
KIAA0198 | |
HGNC (Hugo) | PLAGL2 |
LocusID (NCBI) | 5326 |
Atlas_Id | 41738 |
Location | 20q11.21 [Link to chromosome band 20q11] |
Location_base_pair | Starts at 32192504 and ends at 32207743 bp from pter ( according to hg19-Feb_2009) [Mapping PLAGL2.png] |
Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
DNA/RNA |
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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 |
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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 |
Note | |
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. |
Bibliography |
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Abdollahi A |
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PMID 17063461 |
Identification of a zinc-finger gene at 6q25: a chromosomal region implicated in development of many solid tumors. |
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PMID 9150364 |
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. |
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Involvement of PLAGL2 in activation of iron deficient- and hypoxia-induced gene expression in mouse cell lines. |
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Cbf beta-SMMHC induces distinct abnormal myeloid progenitors able to develop acute myeloid leukemia. |
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A zinc-finger protein, PLAGL2, induces the expression of a proapoptotic protein Nip3, leading to cellular apoptosis. |
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The Journal of biological chemistry. 2002 ; 277 (18) : 15851-15858. |
PMID 11832486 |
Tip60 modulates PLAGL2-mediated transactivation by acetylation. |
Ning J, Zheng G, Yang YC |
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PMID 17551969 |
Cloning and embryonic expression of zebrafish PLAG genes. |
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Regulation of apoptosis and cell cycle arrest by Zac1, a novel zinc finger protein expressed in the pituitary gland and the brain. |
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PMID 10646861 |
Pleiomorphic adenoma gene-like-2, a zinc finger protein, transactivates the surfactant protein-C promoter. |
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American journal of respiratory cell and molecular biology. 2005 ; 32 (1) : 35-43. |
PMID 15361364 |
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 |
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 |
Citation |
This paper should be referenced as such : |
Abdollahi, A |
PLAGL2 (pleomorphic adenoma gene-like 2) |
Atlas Genet Cytogenet Oncol Haematol. 2008;12(5):382-384. |
Free journal version : [ pdf ] [ DOI ] |
On line version : http://AtlasGeneticsOncology.org/Genes/PLAGL2ID41738ch20q11.html |
External links |
REVIEW articles | automatic search in PubMed |
Last year publications | automatic search in PubMed |
© Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Thu Feb 14 17:25:29 CET 2019 |
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