PLAGL2 controls the stability of Pirh2, an E3 ubiquitin ligase for p53.
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.
Zheng
Gang
G
Department of Pharmacology and Cancer Center, School of Medicine, Case Western Reserve University, 2109 Adelbert Road, W353, Cleveland, OH 44106, USA.
Ning
Jinying
J
Yang
Yu-Chung
YC
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D004268:DNA-Binding Proteins; C114598:PLAGL2 protein, human; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C485369:RCHY1 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex