Paternally-expressed gene 3 protein (PEG3)

Paternally-expressed gene 3 protein (PEG3) is a large, multifunctional, paternally imprinted transcription factor encoded by the PEG3 gene, which is expressed exclusively from the paternal allele[3][1][6]. It is characterized by twelve C2H2-type Krüppel zinc finger domains and an N-terminal SCAN domain that facilitates homo- and heterodimerization, essential for its combinatorial regulation of target genes[1][7]. PEG3 regulates gene expression by binding DNA in a sequence-specific manner and primarily functions as a transcriptional repressor for its downstream genes, including other imprinted loci[5][1]. PEG3 participates in diverse biological processes such as fetal growth control, maternal and nurturing behavior, autophagy, apoptosis via p53, repression of Wnt/β-catenin signaling, regulation of mitochondrial genes, and metabolic reprogramming[2][5][4]. It is a critical tumor suppressor frequently dysregulated in cancer through epigenetic silencing (hypermethylation), and its loss is implicated in multiple human malignancies[2][4][6]. PEG3 is also recognized as a marker of competent self-renewing adult stem cells, and its proper regulation is required for cell differentiation and developmental processes[4]. PEG3 can interact with proteins such as SIAH1, TRAF2, and β-catenin, modulating key signaling pathways in cell survival, death, and metabolism[1][3]. Despite its importance in development and disease, PEG3 is not currently considered a direct pharmaceutical target, and no drugs are known to act on PEG3 directly. Its epigenetic status and loss of expression provide potentially valuable biomarkers for cancer prognosis and patient selection[2][6]. No specific safety concerns exist tied to direct targeting, though dysregulation of PEG3 or therapies impacting imprinting could have pleiotropic developmental and oncogenic risks.

Other names

Paternally-expressed gene 3 proteinPEG3KIAA0287ZSCAN24ZKSCAN22ZNF904Zinc finger and SCAN domain-containing protein 24PW1Kruppel-type zinc finger protein