Ask about this productRelated genes to: Pa2g4 antibody
- Gene:
- PA2G4 NIH gene
- Name:
- proliferation-associated 2G4
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 12q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1996-10-26
- Date modifiied:
- 2015-11-09
Related products to: Pa2g4 antibody
Related articles to: Pa2g4 antibody
- Branchio-oto-renal (BOR) syndrome is an autosomal dominant condition characterized by variable malformations including hearing loss and renal dysfunction. Variants in SIX1 or its activating co-factor EYA1 are causative in about 50% of patients. Some patients carrying BOR variants also present with craniosynostosis, indicating that cranial skeletal dysmorphologies could be an under-diagnosed feature. To date, most studies on the role of SIX1 have focused on its role in the cranial placode-based development of the inner ear, whereas its role in the neural crest cells of the mandibular arch, which will give rise to the jaws and middle ear ossicles, is less well characterized. Here, we present novel expression profiles of three putative SIX1 co-factors (PA2G4, MCRS1, and SOBP) in the developing mouse first pharyngeal arch and tooth. SIX1 colocalizes with PA2G4, MCRS1, and SOBP within the oral domain of the mandibular arch and during odontogenesis, although each exhibits a distinct expression pattern. Functional analyses revealed that SOBP binds SIX1, EYA1, and EYA2 and represses both SIX1 + EYA1 and SIX1 + EYA2 transcriptional activity, whereas MCRS1 binds only SIX1 and selectively represses SIX1 + EYA2 activity. In contrast, PA2G4 does not bind SIX1, yet modulates SIX1 + EYA2 activity. We further show that SIX1 is required for proper expression of Pa2g4, Mcrs1, and Sobp in the mouse mandibular arch. Collectively, these results demonstrate that regulation of SIX1 + EYA transcriptional activity is highly context dependent, occurs through both direct and indirect mechanisms, and differs between SIX1 + EYA1 and SIX1 + EYA2 complexes. These findings reveal species-specific differences and uncover a level of regulatory complexity not previously identified in Xenopus studies. - Source: PubMed
Publication date: 2026/07/16
Jourdeuil KarynChukwuocha KelechiGafurova JasminaBen-Mayor AshleyMoody Sally ATavares Andre L P - Neuroblastoma (NB), the most prevalent extracranial solid tumor in children, exhibits high mortality. This study investigated the function and underlying mechanisms of HACE1 in NB pathogenesis. NB tumor tissues and matched adjacent normal tissues were collected, and human NB cell lines SK-N-AS and SK-N-BE2 were used. Cell migration and invasion capacities were evaluated using wound healing and Transwell assays. Cell apoptosis was measured using TdT-mediated dUTP Nick-end Labeling staining. The HACE1 in vivo function was validated using a xenograft mouse model. The results demonstrated that HACE1 expression was downregulated in NB tissues compared with normal tissues. HACE1 overexpression suppressed chemoresistance, migration, and invasion in NB cells; mechanistically, HACE1 bound to PKN1 and promoted its destabilization. The effects of HACE1 knockdown were reversed by the co-knockdown of PKN1. Furthermore, PKN1 bound to and phosphorylated PA2G4 at the T261 residue. Functional assays demonstrated that overexpression of wild-type (WT) PA2G4 promoted cell migration, invasion, and chemoresistance, which were attenuated by the T261A mutation (a non-phosphorylation mimic) but further potentiated by the T261E mutation (a phosphorylation mimic). PKN1 overexpression enhanced the oncogenic functions of WT PA2G4 but not those of the T261A mutant. Finally, the anti-tumor effect of HACE1 was confirmed in vivo. Collectively, this study demonstrates that HACE1 suppresses NB cell migration, invasion, and chemoresistance by destabilizing PKN1, thereby preventing PKN1 from phosphorylating and activating PA2G4. Our findings elucidate a novel HACE1/PKN1/PA2G4 signaling axis in NB progression, expanding the understanding of NB pathogenesis and highlighting the axis's potential as a therapeutic target. - Source: PubMed
Publication date: 2026/06/25
Chen HonghaoZhang ZhuorongHuang FangyuanXiao YueZheng YongqinZhang ZhengtaoXia HuiminHe Hanzhong - - Source: PubMed
Publication date: 2026/05/20
D'Oria FrancescoCostanzo Antonio - Liver hepatocellular carcinoma (LIHC) is a common malignancy, yet the core genes driving its progression and potential therapeutic targets remain insufficiently explored. Ribosome biogenesis (RB) is a critical biological process linked to various cancers; however, its systematic role in LIHC remains unclear. - Source: PubMed
Publication date: 2026/05/14
Qi YajieLi KunLi PinchengYan JianyuFeng ShuyueWan DanDu KeLiang XiaoYang FanZhou ErzhengHuang NaWang QianLiu Nanbin - Nanoplastics (NPs) exhibit neurotoxicity, yet the precise molecular mechanisms remain elusive. In this study, we established a human-relevant polystyrene nanoplastics (PS-NPs, 50 mg kg) oral exposure model in C57BL/6 mice in vivo and a neuro-immune microglial-neuron co-culture system (HMC-3/SH-SY5Y cells) in vitro to dissect these mechanisms. We demonstrate that PS-NPs exposure triggers microglial M1 activation and drives neuronal senescence. Mechanistically, PS-NPs activate the protein phosphatase 2A (PP2A)-B56γ subunit, which selectively dephosphorylates the ribosome biogenesis regulator ErbB3-binding protein 1 (Ebp1) at Ser335. This post-translational modification reduces Ebp1 nucleolar localization, suppresses 47S pre-ribosomal RNA transcription, and induces nucleolar stress. Consequently, the p53/p21 pathway is engaged, promoting neuronal senescence. Pharmacological inhibition of PP2A with LB-100 restored ribosome biogenesis, prevented neuronal senescence, and rescued cognitive deficits and neurodegenerative phenotypes in PS-NP-exposed mice. This is the first study to identify the PP2A-B56γ-p-Ebp1-ribosome biogenesis axis as a novel cascade mechanism driving PS-NP-induced neuronal senescence. Our findings offer a targetable strategy to mitigate nanoplastics-associated neurodegeneration. - Source: PubMed
Publication date: 2026/05/05
Gao Yun-LuWang Ming-ZhuWang Lei-LeiDu Ze-BangXie Yu-HanXu Wen-QiWang Yu-HanLi Ruo-HanGuo Dong-BeiZheng Han-YingYao You-LiangSong Ya-BinLin Zhong-NingLin Yu-Chun