Gene Symbol: CNOT2
Description: CCR4-NOT transcription complex subunit 2
Alias: CDC36, HSPC131, NOT2, NOT2H, CCR4-NOT transcription complex subunit 2, CCR4-associated factor 2, negative regulator of transcription 2
Species: human
Products:     CNOT2

Top Publications

  1. Smid M, Wilting S, Uhr K, Rodríguez González G, de Weerd V, Prager Van der Smissen W, et al. The circular RNome of primary breast cancer. Genome Res. 2019;: pubmed publisher
    ..We confirmed the presence of circRNAs of CNOT2, CREBBP and RERE in an independent pool of primary breast cancers...
  2. Bhaskar V, Basquin J, Conti E. Architecture of the ubiquitylation module of the yeast Ccr4-Not complex. Structure. 2015;23:921-928 pubmed publisher
    ..The structural and biochemical data show how Not1 can incorporate both the ubiquitylation module and the Not2-Not3/5 module concomitantly in the Ccr4-Not complex.
  3. Vicente C, Stirparo R, Demeyer S, de Bock C, Gielen O, Atkins M, et al. The CCR4-NOT complex is a tumor suppressor in Drosophila melanogaster eye cancer models. J Hematol Oncol. 2018;11:108 pubmed publisher
    ..Our data show that knockdown of Not3, the structural components Not1/Not2, and the deadenylases twin/Pop2 all result in increased tumor formation...
  4. Faraji F, Hu Y, Yang H, Lee M, Winkler G, Hafner M, et al. Post-transcriptional Control of Tumor Cell Autonomous Metastatic Potential by CCR4-NOT Deadenylase CNOT7. PLoS Genet. 2016;12:e1005820 pubmed publisher
    ..Previously, we demonstrated that the CCR4-NOT scaffold component Cnot2 is an inherited metastasis susceptibility gene...
  5. Rodriguez Gil A, Ritter O, Hornung J, Stekman H, Kruger M, Braun T, et al. HIPK family kinases bind and regulate the function of the CCR4-NOT complex. Mol Biol Cell. 2016;27:1969-80 pubmed publisher
    ..Down-regulation or knockout of the CCR4-NOT complex member CNOT2 leads to reduced HIPK2 protein levels without affecting the expression level of HIPK1 or HIPK3...
  6. Wang Z, Cheng Y, Abraham J, Yan R, Liu X, Chen W, et al. RNA sequencing of esophageal adenocarcinomas identifies novel fusion transcripts, including NPC1-MELK, arising from a complex chromosomal rearrangement. Cancer. 2017;123:3916-3924 pubmed publisher
    ..8%, and CCR4-NOT transcription complex subunit 2 (CNOT2)-chromosome 12 open reading frame 49 (C12orf49) in 1 of 55 or 1.8%...
  7. Rodriguez Gil A, Ritter O, Saul V, Wilhelm J, Yang C, Grosschedl R, et al. The CCR4-NOT complex contributes to repression of Major Histocompatibility Complex class II transcription. Sci Rep. 2017;7:3547 pubmed publisher
    ..Here we performed a systematic and comparative analysis of cells where the CCR4-NOT subunits CNOT1, CNOT2 or CNOT3 were individually downregulated using doxycycline-inducible shRNAs...
  8. Alesi V, Loddo S, Grispo M, Riccio S, Montella A, Dallapiccola B, et al. Reassessment of the 12q15 deletion syndrome critical region. Eur J Med Genet. 2017;60:220-223 pubmed publisher
    ..We identified by microarray analysis a new case of 12q15 deletion. Our patient clinical features allow the refinement of the SRO to CNOT2, KCNMB4, and PTPRB genes, improving genotype-phenotype correlations.
  9. Dias L, Thodima V, Friedman J, Ma C, Guttapalli A, Mendiratta G, et al. Cross-platform assessment of genomic imbalance confirms the clinical relevance of genomic complexity and reveals loci with potential pathogenic roles in diffuse large B-cell lymphoma. Leuk Lymphoma. 2016;57:899-908 pubmed publisher
    ..of these criteria to independent datasets revealed novel candidate genes with coordinated expression, such as CNOT2, potentially with pathogenic roles...

More Information


  1. Sohn E, Jung D, Lee H, HAN I, Lee J, Lee H, et al. CNOT2 promotes proliferation and angiogenesis via VEGF signaling in MDA-MB-231 breast cancer cells. Cancer Lett. 2018;412:88-98 pubmed publisher
    Here the underlying role of CNOT2, a subunit of CCR4-NOT complex, was elucidated in cancer progression...
  2. Jayne S, Zwartjes C, van Schaik F, Timmers H. Involvement of the SMRT/NCoR-HDAC3 complex in transcriptional repression by the CNOT2 subunit of the human Ccr4-Not complex. Biochem J. 2006;398:461-7 pubmed
    ..Previously, we showed that promoter targeting of the CNOT2 subunit resulted in strong repression of RNA polymerase II transcription, which was sensitive to the HDAC (histone ..
  3. Zheng X, Dumitru R, Lackford B, Freudenberg J, Singh A, Archer T, et al. Cnot1, Cnot2, and Cnot3 maintain mouse and human ESC identity and inhibit extraembryonic differentiation. Stem Cells. 2012;30:910-22 pubmed publisher
    ..Here, we show that three members of the Ccr4-Not complex, Cnot1, Cnot2, and Cnot3, play critical roles in maintaining mouse and human ESC identity as a protein complex and inhibit ..
  4. Albert T, Lemaire M, van Berkum N, Gentz R, Collart M, Timmers H. Isolation and characterization of human orthologs of yeast CCR4-NOT complex subunits. Nucleic Acids Res. 2000;28:809-17 pubmed
    ..Here we report the isolation of cDNAs encoding human NOT2, NOT3, NOT4 and a CAF1-like factor, CALIF...
  5. Shi J, Nelson M. The cyclin-dependent kinase 11 interacts with NOT2. Biochem Biophys Res Commun. 2005;334:1310-6 pubmed
    ..We used a yeast two-hybrid screening strategy and identified NOT2 as an interacting partner of caspase-processed C-terminal kinase domain of CDK11 (CDK11(p46))...
  6. Winkler G, Mulder K, Bardwell V, Kalkhoven E, Timmers H. Human Ccr4-Not complex is a ligand-dependent repressor of nuclear receptor-mediated transcription. EMBO J. 2006;25:3089-99 pubmed
    ..These findings define a function for the human Ccr4-Not complex as a transcriptional repressor of nuclear receptor signalling that is relevant for the understanding of molecular pathways involved in cancer. ..
  7. Miyasaka T, Morita M, Ito K, Suzuki T, Fukuda H, Takeda S, et al. Interaction of antiproliferative protein Tob with the CCR4-NOT deadenylase complex. Cancer Sci. 2008;99:755-61 pubmed publisher
    ..These results suggest that the antiproliferative activity of Tob is shown post-transcriptionally by controlling the stability of the target mRNAs in addition to its involvement in transcriptional regulation, reported previously. ..
  8. Braun J, Huntzinger E, Fauser M, Izaurralde E. GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA targets. Mol Cell. 2011;44:120-33 pubmed publisher
  9. Zwartjes C, Jayne S, van den Berg D, Timmers H. Repression of promoter activity by CNOT2, a subunit of the transcription regulatory Ccr4-not complex. J Biol Chem. 2004;279:10848-54 pubmed
    ..In this experimental setup we found that the CNOT2 and CNOT9(hRcd1/hCaf40) subunits act as repressors of reporter gene activity...
  10. Ahmeti K, Ajroud Driss S, Al Chalabi A, Andersen P, Armstrong J, Birve A, et al. Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1. Neurobiol Aging. 2013;34:357.e7-19 pubmed publisher
    ..Identifying the underlying pathways influencing susceptibility to and age at onset of ALS may provide insight into the pathogenic mechanisms and motivate new pharmacologic targets for this fatal neurodegenerative disease. ..
  11. Rambout X, Detiffe C, Bruyr J, Mariavelle E, Cherkaoui M, Brohée S, et al. The transcription factor ERG recruits CCR4-NOT to control mRNA decay and mitotic progression. Nat Struct Mol Biol. 2016;23:663-72 pubmed publisher recruited to mRNAs via interaction with the RNA-binding protein RBPMS, and it promotes mRNA decay by binding CNOT2, a component of the CCR4-NOT deadenylation complex...
  12. Fabian M, Cieplak M, Frank F, Morita M, Green J, Srikumar T, et al. miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT. Nat Struct Mol Biol. 2011;18:1211-7 pubmed publisher
    ..Thus, GW182 serves as both a platform that recruits deadenylases and as a deadenylase coactivator that facilitates the removal of the poly(A) tail by CCR4-NOT. ..
  13. Ito K, Inoue T, Yokoyama K, Morita M, Suzuki T, Yamamoto T. CNOT2 depletion disrupts and inhibits the CCR4-NOT deadenylase complex and induces apoptotic cell death. Genes Cells. 2011;16:368-79 pubmed publisher
    ..The roles of the other subunits remain obscure. Here, we show that CNOT2 depletion by siRNA induces apoptosis...
  14. Denis C, Chen J. The CCR4-NOT complex plays diverse roles in mRNA metabolism. Prog Nucleic Acid Res Mol Biol. 2003;73:221-50 pubmed
    ..Finally, the functional diversity of the CCR4-NOT complex is related to its mediating responses from a number of cellular signaling pathways. ..
  15. Boland A, Chen Y, Raisch T, Jonas S, Kuzuoğlu Öztürk D, Wohlbold L, et al. Structure and assembly of the NOT module of the human CCR4-NOT complex. Nat Struct Mol Biol. 2013;20:1289-97 pubmed publisher
    ..We report the crystal structure of the human NOT module formed by the CNOT1, CNOT2 and CNOT3 C-terminal (-C) regions...
  16. Lau N, Kolkman A, van Schaik F, Mulder K, Pijnappel W, Heck A, et al. Human Ccr4-Not complexes contain variable deadenylase subunits. Biochem J. 2009;422:443-53 pubmed publisher
    ..Taken together, human Ccr4-Not complexes are heterogeneous in composition owing to differences in their deadenylase subunits, which may reflect the multi-functionality of these complexes in cellular processes. ..
  17. Morita M, Suzuki T, Nakamura T, Yokoyama K, Miyasaka T, Yamamoto T. Depletion of mammalian CCR4b deadenylase triggers elevation of the p27Kip1 mRNA level and impairs cell growth. Mol Cell Biol. 2007;27:4980-90 pubmed
    ..Thus, CCR4b may be involved in various cellular events that include cell proliferation. ..