Oncogene database

5326

PLAGL2

pleiomorphic adenoma gene-like 2;PLAGL2;pleiomorphic adenoma gene-like 2

C2H2-type zinc finger protein|pleiomorphic adenoma-like protein 2|zinc finger protein PLAGL2

20q11.21

protein-coding

Recurrent chromosomal rearrangements are associated with the development of acute myeloid leukemia (AML). The frequent inversion of chromosome 16 creates the CBFB-MYH11 fusion gene that encodes the fusion protein CBFbeta-SMMHC. This fusion protein inhibits the core-binding factor (CBF), resulting in a block of hematopoietic differentiation, and induces leukemia upon the acquisition of additional mutations. A recent genetic screen identified Plag1 and Plagl2 as CBF beta-SMMHC candidate cooperating proteins. In this study, we demonstrate that Plag1 and Plagl2 independently cooperate with CBF beta-SMMHC in vivo to efficiently trigger leukemia with short latency in the mouse. In addition, Plag1 and Plagl2 increased proliferation by inducing G1 to S transition that resulted in the expansion of hematopoietic progenitors and increased cell renewal in vitro. Finally, PLAG1 and PLAGL2 expression was increased in 20% of human AML samples. Interestingly, PLAGL2 was preferentially increased in samples with chromosome 16 inversion, suggesting that PLAG1 and PLAGL2 may also contribute to human AML. Overall, this study shows that Plag1 and Plagl2 are novel leukemia oncogenes that act by expanding hematopoietic progenitors expressing CbF beta-SMMHC.

PLAGL2 (Pleomorphic Adenoma Gene Like 2) is an oncoprotein involved in various malignancies including lipoblastomas, hepatoblastomas, and acute myeloid leukemia. Although PLAGL2 is known to mainly act as a transcription factor, other functions which may contribute to its oncogenic potential are not clear. Pirh2 (P53 induced RING-H2 protein) is a p53 inducible E3 ligase involved in the ubiquitination of p53, while the mechanisms to regulate its activities are largely unknown. In this study, we show for the first time that Pirh2 forms dimers through its N- and C-terminus in cells and Pirh2 dimers interact with PLAGL2. The interaction between PLAGL2 and Pirh2 dimers prevents proteasomal degradation of Pirh2. This study thus uncovers a novel function of PLAGL2 as an oncoprotein through regulating the stability of Pirh2. Given the importance of Pirh2 in regulating p53 stability, its interaction with PLAGL2 may provide valuable therapeutic targets in treating Pirh2-overexpression malignancies.

Numerous previous studies have revealed that pleomorphic adenoma gene-like 2 (PLAGL2) is a transcription factor that is active in cancer progression. The aim of this study was to investigate the role of PLAGL2 in the development, progression and prognosis of gastrointestinal cancer. Immunohistochemical analysis revealed that PLAGL2 was expressed in gastrointestinal tumors and adjacent normal tissues. The expression of PLAGL2 was significantly higher in 225 colorectal cancer tissues than in 66 adjacent non-tumor tissues (P = 0.037). However, expression was not significantly different between 286 gastric tumors and 57 adjacent non-tumor tissues (P = 0.352). Moreover, the PLAGL2 expression level significantly correlated with the depth of tumor invasion in colorectal cancer (P = 0.030). However, the PLAGL2 expression level significantly correlated with tumor size in gastric cancer (P = 0.046). Furthermore, we performed survival analyses and found that neither higher nor lower PLAGL2 expression was a prognostic factor in gastrointestinal cancer. Our findings indicate that PALGL2 serves as a tumor oncoprotein in the development and progression of colorectal cancer. However, the role of this protein in the development, progression and prognosis of gastric cancer is uncertain. Further investigation into the molecular mechanisms of PLAGL2 activity in gastrointestinal cancer is warranted.