Ask about this productRelated genes to: CNOT6 antibody
- Gene:
- CNOT6 NIH gene
- Name:
- CCR4-NOT transcription complex subunit 6
- Previous symbol:
- -
- Synonyms:
- CCR4, KIAA1194, Ccr4a
- Chromosome:
- 5q35.3
- Locus Type:
- gene with protein product
- Date approved:
- 2001-03-30
- Date modifiied:
- 2015-11-12
Related products to: CNOT6 antibody
Related articles to: CNOT6 antibody
- Postnatal growth and development require precise coordination of growth and metabolism to meet the biosynthetic and energetic demands of rapidly expanding organs. Fibroblast growth factor 21 (FGF21) serves as a key endocrine regulator linking nutrient availability to systemic growth control in early life and metabolic homeostasis in adulthood. Here, we identify the CCR4-NOT deadenylase complex subunit CNOT6, but not its paralog CNOT6L, as an essential post-transcriptional regulator of neonatal growth and metabolism. Loss of results in severe growth retardation, multi-organ hypoplasia, and increased perinatal mortality. Surviving knockout mice display markedly reduced body and organ size that gradually normalizes by adulthood, indicating developmental compensation. Mechanistically, deficiency elevates hepatic mRNA expression, suppresses the IGF1-IGFBP1 axis, and reprograms liver transcriptional networks controlling lipid and glucose metabolism and apoptosis. These changes are accompanied by increased ketone body production, suggesting enhanced fatty acid oxidation. Together, our findings uncover a previously unrecognized role of CNOT6 in limiting FGF21 expression to preserve anabolic metabolism during the neonatal period. This work establishes the CNOT6-FGF21 axis as a molecular checkpoint that couples mRNA decay with hormonal and metabolic coordination required for healthy postnatal growth. - Source: PubMed
Publication date: 2026/02/18
Saeed MoawizZang MengweiGius DavidKatsumura SakieMorita Masahiro - Elevated lactate is associated with vascular endothelial dysfunction, a factor that can contribute to organ failure in sepsis. However, the specific mechanisms involved have yet to be fully elucidated. Here, we investigated the role of enolase 1 (ENO1) lactylation in modulating the functions of endothelial cells (ECs) in sepsis pathogenesis. - Source: PubMed
Xie XueruLiu TingyanZhang CaiyanCheng YeGao YajingXiao WenfengGuo HaiyanZhou YutongYu YaweiWang KexinLin YinghongXiao LishengZhang YingyingYang WeiguoYan GangfengLu GuopingZhou Yufeng - The human Ccr4-Not complex is a central regulator of post-transcriptional gene regulation, impacting on translation and mRNA degradation. In mRNA degradation, Ccr4-Not participates in the shortening of the mRNA poly(A)-tail via two catalytic subunits. The Caf1 nuclease is encoded by the highly similar paralogues CNOT7 or CNOT8. In addition to its poly(A)-specific ribonuclease activity, this subunit also provides a structural role by binding Ccr4, the second catalytic nuclease subunit encoded by the paralogues CNOT6 or CNOT6L. To facilitate investigations into the roles of the Caf1 subunit, and to complement genetic tools, we set out to identify inhibitors of the enzymatic activity of Caf1/CNOT7. To this end, we screened a library of 10,880 chemically diverse, drug-like compounds using a fluorescence-based biochemical assay. This effort led to the discovery of 15 inhibitors of Caf1/CNOT7 with biochemical IC values below 25 μM. Molecular docking was performed to explore potential binding modes of these compounds. The compounds reported here may be useful to differentiate between catalytic and non-catalytic roles of Caf1/CNOT7. In addition, they may be valuable starting points for the development of more potent inhibitors of the Caf1/CNOT7 poly(A)-selective ribonuclease. - Source: PubMed
Publication date: 2025/11/06
Kaur IshwinderHashmi LubnaFischer Peter MWinkler Gerlof Sebastiaan - Heart failure is rapidly increasing and is a growing burden on human health and the economy in the world. The functional role of mRNA regulation in the pathogenesis of heart failure remains to be elucidated. Carbon catabolite repression 4-negative on TATA-less complex is a multisubunit protein complex that deadenylates mRNA, a process of exonuclease-mediated degradation of mRNA poly(A) tail. Here we show the cardiac protective roles of deadenylase subunit CNOT6L against cardiac stress. After 2 weeks of transverse aortic constriction (TAC)-induced pressure overload, expression of CNOT6L deadenylase subunit was significantly upregulated in the mouse hearts. When CNOT6L gene was genetically deleted, the mice exhibited marked decline of left ventricular contractility and enhancement of fibrosis at 2 weeks after TAC. Transcriptome analyses elucidated that CNOT6L targets tenascin-C mRNA, which stimulates tissue fibrosis and inflammation. CNOT6L deletion markedly upregulated tenascin-C expression in cardiac fibroblasts. Poly(A) tail length and luciferase reporter analyses revealed that CNOT6L catalyzes deadenylation of tenascin-C mRNA likely through interaction with the cis-element in its 3'-untranslated region. Double knockout of tenascin-C and CNOT6L ameliorated cardiac fibrosis and dysfunction in single CNOT6 knockout mice under TAC or chronic infusion of angiotensin II. Thus, CNOT6L deadenylase prevents the progression of heart failure through downregulation of the expression of tenascin-C in cardiac fibroblasts, implicating a potential therapeutic strategy of targeting mRNA deadenylation. SIGNIFICANCE STATEMENT: To our knowledge, this study provides the first evidence that posttranscriptional regulation of tenascin-C expression in cardiac fibroblasts, including cell-type-specific roles of CNOT6L-mediated mRNA deadenylation, is crucial to maintain heart functions against pressure overload stress or angiotensin II-induced hypertension, implicating a potential therapeutic strategy of targeting mRNA deadenylation. - Source: PubMed
Publication date: 2024/11/30
Sato TerukiYamaguchi TomokazuMinato TakafumiHoshizaki MidoriYamamoto AyahaMorita MasahiroSuzuki ToruFujio YasushiImai YumikoSuzuki YutakaYamamoto TadashiWatanabe HiroyukiKuba Keiji - The eukaryotic CCR4-NOT deadenylase complex is a highly conserved regulator of mRNA metabolism that influences the expression of the complete transcriptome, representing a prime target for a generalist bacterial pathogen. We show that a translocated bacterial effector protein, PieF (Lpg1972) of , directly interacts with the CNOT7/8 nuclease module of CCR4-NOT, with a dissociation constant in the low nanomolar range. PieF is a robust inhibitor of the DEDD-type nuclease, CNOT7, acting in a stoichiometric, dose-dependent manner. Heterologous expression of PieF phenocopies knockout of the CNOT7 ortholog (POP2) in , resulting in 6-azauracil sensitivity. In mammalian cells, expression of PieF leads to a variety of quantifiable phenotypes: PieF silences gene expression and reduces mRNA steady-state levels when artificially tethered to a reporter transcript, and its overexpression results in the nuclear exclusion of CNOT7. PieF expression also disrupts the association between CNOT6/6L EEP-type nucleases and CNOT7. Adding to the complexities of PieF activity , we identified a separate domain of PieF responsible for binding to eukaryotic kinases. Unlike what we observe for CNOT6/6L, we show that these interactions can occur concomitantly with PieF's binding to CNOT7. Collectively, this work reveals a new, highly conserved target of effectors and suggests a mechanism by which the pathogen may be modulating host mRNA stability and expression during infection. - Source: PubMed
Publication date: 2024/12/19
Mount Harley O'ConnorUrbanus Malene LZangari FrancescoGingras Anne-ClaudeEnsminger Alexander W