Ask about this productRelated genes to: CNOT2 antibody
- Gene:
- CNOT2 NIH gene
- Name:
- CCR4-NOT transcription complex subunit 2
- Previous symbol:
- NOT2
- Synonyms:
- CDC36, NOT2H
- Chromosome:
- 12q15
- Locus Type:
- gene with protein product
- Date approved:
- 1996-07-19
- Date modifiied:
- 2015-11-12
Related products to: CNOT2 antibody
Related articles to: CNOT2 antibody
- Cornin, a bioactive iridoid glycoside isolated from Cornus officinalis, has been reported to exhibit cardioprotective and pro-apoptotic activities. However, its antitumor mechanism in cervical cancer remains largely unknown. In this study, we investigated the antiangiogenic and anti-invasive effects of Cornin, focusing on the CNOT2-VEGF signaling axis. Cornin showed limited cytotoxicity in SiHa, HeLa, and CaSki cervical cancer cells but significantly downregulated CNOT2, N-cadherin, VEGF, and Snail expression in HeLa and SiHa cells. Functional analyses revealed that CNOT2 silencing suppressed wound healing activity, while Cornin treatment markedly inhibited cell migration, invasion, and VEGF secretion in HeLa cells. VEGF luciferase reporter and cycloheximide chase assays confirmed that Cornin reduced VEGF transcription and protein stability in a time-dependent manner. Furthermore, Cornin inhibited tube formation in HUVECs and angiogenesis in the chick chorioallantoic membrane (CAM) model. TCGA analysis showed that CNOT2 expression was elevated in cervical cancer tissues and positively correlated with VEGF expression (r = 0.35). This association was further supported by immunoprecipitation analysis demonstrating a physical interaction between CNOT2 and VEGF in HeLa cells. Mechanistically, ectopic CNOT2 expression upregulated VEGF, whereas its depletion suppressed VEGF expression. Collectively, these findings highlight the CNOT2-VEGF axis as a crucial mediator in antiangiogenic and anti-invasive effects of Cornin in cervical cancer, suggesting Cornin as a potent natural inhibitor of tumor angiogenesis and invasion. - Source: PubMed
Publication date: 2026/04/27
Cho Ah ReumPark Su-YeonSim Deok YongAhn Chi-HoonKim BongleeShim Bum-SangKim Sung-Hoon - A number of published studies suggest that HIV infection accelerates epigenetic ageing. The main aim of this study was to ascertain if HIV infection is an independent factor leading to DNA hypomethylation and accelerating epigenetic ageing in men successfully treated with integrase inhibitor (INSTI)-based combined antiretroviral therapy (cART). Forty-eight (48) men living with HIV receiving INSTI-based cART and fifty (50) uninfected men in the control group were included. All participants filled out a questionnaire probing into lifestyle factors. Global and site-specific DNA methylation and expression of methyltransferase genes were examined in all participants. As well, all patients underwent basic laboratory blood tests. The results were analysed using statistical and machine learning methods. We found a strong association between HIV infection and global DNA hypomethylation as well as significant association with higher expression of the methyltransferase gene . However, there was no association with DNA methylation levels of CNOT2, DPP6, FOXG1 and NPTX2 genes or expression levels of and . The results confirm that in men successfully treated with INSTI-based cART, HIV infection is an independent factor causing global DNA hypomethylation and increased expression and thus accelerating epigenetic ageing. - Source: PubMed
Publication date: 2026/02/02
Bożejko MateuszMałodobra-Mazur MałgorzataGnatowski AndrzejOłdakowska MonikaSzymczak AleksandraSzetela BartoszCiepłucha HubertZińczuk AleksanderKnysz Brygida - Although benzyl isothiocyanate (BITC), a major compound found in cruciferous vegetables, has been reported to exert antitumor effects in various cancers, its apoptotic mechanism remains unclear. This study aimed to elucidate the apoptotic mechanism of BITC by investigating its role in inhibiting Warburg effect in hepatocellular carcinoma (HCC) cells. BITC suppressed cell proliferation, increased the sub-G1 population, Annexin V/PI and reduced the expression of pro-poly (ADP-ribose) polymerase (pro-PARP), pro-caspase-3, CCR4-NOT transcription complex subunit 2 (CNOT2), c-Myc, signal transducer and activator of transcription 3 (STAT3), and phosphorylated Janus kinase 1 (p-JAK1) in SK-Hep1 and Huh7 HCC cell lines. Notably, knockdown of STAT3 or its upstream regulator CNOT2 further enhanced BITC-induced apoptosis, as evidenced by decreased pro-PARP and pro-caspase-3 expression in SK-Hep1 cells. Additionally, BITC attenuated the expression of hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and lactate dehydrogenase (LDH) along with reduced LDH production and glucose in SK-Hep1 and Huh7 cells. However, treatment of pyruvate or overexpression of CNOT2 or c-Myc reversed the capacity of BITC to reduce the expression of HK2, pro-caspase-3, and pro-PARP in SK-Hep1 cells. Immunoprecipitation assays further revealed that BITC disrupted the interactions between CNOT2 and STAT3 or c-Myc. Collectively, these findings suggest that the CNOT2/c-Myc/STAT3 signaling axis plays a critical role in glycolysis mediated apoptosis of BITC in HCC cells. - Source: PubMed
Publication date: 2026/02/02
Koh WonilPark Su-YeonKim BongleeShim Bum-SangKim Sung-Hoon - Pumilio (PUM) proteins are conserved RNA-binding proteins that control mRNAs involved in development, proliferation, and stem cell differentiation. Human PUM1 and PUM2 repress targets by recruiting the CCR4-NOT deadenylase complex through a metazoan-specific N-terminal repression domain (RD3), which is predicted to be intrinsically disordered. Here we dissect RD3 using cell-based reporter assays, protein interaction assays with recombinant proteins, and crosslinking mass spectrometry. We identify multiple short RD3 peptides that are sufficient for repression and bind directly to the C-terminal NOT module of CCR4-NOT, comprising CNOT1, CNOT2, and CNOT3 subunits. Crosslinking reveals numerous mutually exclusive contacts between RD3 and the NOT module, consistent with a multivalent "fuzzy" binding mode in which interactions are not defined by a single sequence or structure. Sequence scrambling shows that the linear amino acid order of RD3 is dispensable, whereas its physicochemical composition, in particular distributed aliphatic and aromatic residues, is essential for repression and CCR4-NOT binding. These findings support a model in which low-affinity, multivalent interactions between intrinsically disordered regions (IDRs) and effector complexes, governed by amino acid composition rather than precise sequence, underlie robust PUM-mediated repression, and exemplify general principles by which IDRs recruit the CCR4-NOT complex to regulate gene expression. - Source: PubMed
Publication date: 2025/12/20
Dunshee Elise BSaladin Brenna ATurner David JQiu ChenDutcher Robert CWilliams Jason GCorbo JoshuaWolcott Olivia RKorte Amanda JHaugen Rebecca JTanaka Hall Traci MValkov EugeneGoldstrohm Aaron C - , a central component of the CCR4-NOT transcription complex subunit 2, plays a pivotal role in the regulation of gene expression and metabolism. is involved in various cellular processes, including transcriptional regulation, mRNA deadenylation, and the modulation of mRNA stability. specifically contributes to the structural integrity and enzymatic activity of the CCR4-NOT complex with transcription factors and RNA-binding proteins. Recent studies have elucidated its involvement in cellular differentiation, immune response modulation, and the maintenance of genomic stability. Abnormal regulation of has been implicated in a spectrum of pathological conditions, including oncogenesis, neurodegenerative disorders, and metabolic dysfunctions. This review comprehensively examines the interplay between and p53, elucidating their collaborative and antagonistic interactions in various cellular contexts. is primarily involved in transcriptional regulation, mRNA deadenylation, and the modulation of mRNA stability, thereby influencing diverse biological processes such as cell proliferation, apoptosis, and differentiation. Conversely, p53 is renowned for its role in maintaining genomic integrity, inducing cell cycle arrest, apoptosis, and senescence in response to cellular stress and DNA damage. Emerging evidence suggests that can modulate p53 activity through multiple mechanisms, including the regulation of p53 mRNA stability and the modulation of p53 target gene expression. The dysregulation of and p53 interactions has been implicated in the pathogenesis and progression of various cancers, highlighting their potential as therapeutic targets. Additionally, regulates c-Myc, a well-known oncogene, in cancer cells. This review shows the essential roles of in maintaining cancer cellular homeostasis and explores its interactions within the CCR4-NOT complex that influence transcriptional and post-transcriptional regulation. Furthermore, we investigate the potential of as a biomarker and therapeutic target across various disease states, highlighting its significance in disease progression and treatment responsiveness. - Source: PubMed
Publication date: 2025/08/04
Lee JihyunKim Ju-HaLee Yu JinOh Je JoungHan Yeo JeongJung Ji Hoon