PA2G4

Last update 08 May 2025

Basic Info

Synonyms

Cell cycle protein p38-2G4 homolog, EBP1, ErbB3-binding protein 1

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Introduction

May play a role in a ERBB3-regulated signal transduction pathway. Seems be involved in growth regulation. Acts a corepressor of the androgen receptor (AR) and is regulated by the ERBB3 ligand neuregulin-1/heregulin (HRG). Inhibits transcription of some E2F1-regulated promoters, probably by recruiting histone acetylase (HAT) activity. Binds RNA. Associates with 28S, 18S and 5.8S mature rRNAs, several rRNA precursors and probably U3 small nucleolar RNA. May be involved in regulation of intermediate and late steps of rRNA processing. May be involved in ribosome assembly. Mediates cap-independent translation of specific viral IRESs (internal ribosomal entry site) (By similarity). Regulates cell proliferation, differentiation, and survival. Isoform 1 suppresses apoptosis whereas isoform 2 promotes cell differentiation (By similarity).

100 Clinical Results associated with PA2G4

100 Translational Medicine associated with PA2G4

0 Patents (Medical) associated with PA2G4

208

Literatures (Medical) associated with PA2G4

01 Mar 2025·Advances in Medical Sciences

Recurrent hepatocellular carcinoma is associated with the enrichment of MYC targets gene sets, elevated high confidence deleterious mutations and alternative splicing of DDB2 and BRCA1 transcripts

Article

Author: Karaosmanoğlu, Oğuzhan

PURPOSERecurrence is the main cause of hepatocellular carcinoma (HCC) related deaths. Underlying recurrence biology can be better understood by comparative analysis of the complete set of transcripts between recurrent and non-recurrent HCC. In this study, transcriptomic data (GSE56545) from 21 male patients diagnosed with either recurrent or non-recurrent HCC were reanalyzed to identify deregulated pathways, somatic mutations, fusion transcripts, alternative splicing events, and the immune context in recurrent HCC.MATERIALS AND METHODSDESeq2 was used for differential expression analysis, Mutect2 for somatic mutation analysis, Arriba and STAR-Fusion for fusion transcript analysis, and rMATs for alternative splicing analysis.RESULTSThe results revealed that MYC targets gene sets (Hallmark_MYC_targets_V1 and Hallmark_MYC_targets_V2) were significantly enriched in recurrent HCC. Among the MYC targets, CBX3, NOP56, CDK4, NPM1, MCM5, MCM4 and PA2G4 upregulation was significantly associated with poor survival. Somatic mutation analysis demonstrated that the numbers of high confidence deleterious mutations were significantly increased in recurrent HCC. Alternative splicing-mediated production of non-functional DDB2 and oncogenic BRCA1 D11q were discovered in recurrent HCC. Finally, CD8⁺ T-cells were significantly decreased in recurrent HCC.CONCLUSIONSThese results indicated that the enrichment of MYC targets gene sets is one of the most critical factors that leads to the development of recurrent HCC. In addition, elevated deleterious mutation numbers and alternative spliced DDB2 and BRCA1 isoforms have been identified as prominent contributors to increasing genomic instability in male patients with recurrent HCC.

01 Feb 2025·Journal of Advanced Research

PA2G4 in health and disease: An underestimated multifunctional regulator

Review

Author: Chen, Xiaoping ; Xiang, Shuai ; Zhang, Bixiang ; Sun, Sheng ; Huang, Zhao ; Wang, Gaocheng ; Jia, Wenlong

BACKGROUNDProliferation-associated protein 2G4 (PA2G4), also known as ErbB3-binding protein 1 (EBP1), is an evolutionarily conserved, ubiquitously expressed, multifunctional factor in health and disease. In recent decades, its role as a sophisticated regulator in a broad range of biological processes has drawn widespread attention from researchers.AIM OF REVIEWWe introduce the molecular structure, functional modules, and post-translational modifications of PA2G4. We further elaborate on its role and function in immune microenvironment modulation, cell growth, neural homeostasis and embryonic development. In particular, we summarize its relevance to tumorigenesis and cancer progression and describe its molecular mechanisms in regulating the hallmarks of cancers. This review aims to provide a comprehensive blueprint of PA2G4 functions and to inspire further basic and translational studies.KEY SCIENTIFIC CONCEPTS OF REVIEWOwing to its versatile domains and motifs, PA2G4 regulates a variety of molecular processes, including transcription, translation, proteostasis and epigenetic modulation, suggesting its critical roles in maintaining homeostasis. There are two isoforms of the PA2G4 protein: PA2G4-p42 and PA2G4-p48. While both isoforms regulate cellular activities, they often exert distinct or even contradictory effects. Dysfunction and aberrant expression of PA2G4 isoforms lead to the occurrence and progression of various diseases, indicating their role as predictive markers or therapeutic targets.

01 Feb 2025·Translational Oncology

Composition analysis and mechanism of Guizhi Fuling capsule in anti-cisplatin-resistant ovarian cancer

Article

Author: Zhang, Rongjin ; Sun, Ye ; Zhang, Yi ; Yan, Yan ; Tian, Dongli ; Li, Yin ; Dou, Lei ; Deng, Lei ; Zhang, Xue ; Li, Fangmei ; Lu, Enting

OBJECTIVECisplatin is the main chemotherapy drug for advanced ovarian cancer, but drug resistance often occurs. The aim of this study is to explore the molecular mechanism by which Guizhi Fuling capsule inhibits cisplatin resistance in ovarian cancer.METHODSFirst, differences in cisplatin resistance, PA2G4 gene expression, migration, and invasion in A2780 cells and A2780/DDP cells were analyzed by qRT-PCR, scratch assay, transwell, immunofluorescence, and western blotting. Then, LC-MS/MS analysis of GFC chemical composition. qRT-PCR, scratch tests, transwell, pseudopodium formation, immunofluorescence, and western blotting were used to explore the mechanism by which GFC inhibited A2780/DDP cell migration and invasion. Finally, the anti-tumor efficacy of GFC was verified by in vivo experiments.RESULTSA2780/DDP cells had a greater ability to migrate and invade compared to their parents. Cell viability experiments showed that the migration and invasion ability of A278/DDP cells were significantly inhibited with the increase of GFC concentration. qRT-PCR results showed that compared with the blank control group, cisplatin group and GFC group, the transcription level of PA2G4 gene in the combination treatment group was significantly reduced. We also found that GFC combined with cisplatin inhibited the PI3K/AKT/GSK-3β signaling pathway by targeting PA2G4 gene expression, inhibited the epithelial-mesenchymal transition signaling pathway, decreased cell adhesion and inhibited the formation of cell pseudopodias.CONCLUSIONGFC combined with cisplatin can target PA2G4 gene to regulate PI3K/AKT/GSK-3β Signaling pathway, inhibiting the invasion and migration of cisplatin resistant A2780/DDP cells in ovarian cancer.

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PA2G4

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