All Outputs (18)

Discovery of Substituted 5-(2-Hydroxybenzoyl)-2-Pyridone Analogues as Inhibitors of the Human Caf1/CNOT7 Ribonuclease (2024)
Journal Article
Kaur, I., Jadhav, G. P., Fischer, P. M., & Winkler, G. S. (2024). Discovery of Substituted 5-(2-Hydroxybenzoyl)-2-Pyridone Analogues as Inhibitors of the Human Caf1/CNOT7 Ribonuclease. Molecules, 29(18), Article 4351. https://doi.org/10.3390/molecules29184351

The Caf1/CNOT7 nuclease is a catalytic component of the Ccr4-Not deadenylase complex, which is a key regulator of post-transcriptional gene regulation. In addition to providing catalytic activity, Caf1/CNOT7 and its paralogue Caf1/CNOT8 also contribu... Read More about Discovery of Substituted 5-(2-Hydroxybenzoyl)-2-Pyridone Analogues as Inhibitors of the Human Caf1/CNOT7 Ribonuclease.

CCR4‐NOT differentially controls host versus virus poly(a)‐tail length and regulates HCMV infection (2023)
Journal Article
Burgess, H. M., Grande, R., Riccio, S., Dinesh, I., Winkler, G. S., Depledge, D. P., & Mohr, I. (2023). CCR4‐NOT differentially controls host versus virus poly(a)‐tail length and regulates HCMV infection. EMBO Reports, 24(12), Article e56327. https://doi.org/10.15252/embr.202256327

Unlike most RNA and DNA viruses that broadly stimulate mRNA decay and interfere with host gene expression, human cytomegalovirus (HCMV) extensively remodels the host translatome without producing an mRNA decay enzyme. By performing a targeted loss-of... Read More about CCR4‐NOT differentially controls host versus virus poly(a)‐tail length and regulates HCMV infection.

Structure and function of molecular machines involved in deadenylation-dependent 5′-3′ mRNA degradation (2023)
Journal Article
Zhao, Q., Pavanello, L., Bartlam, M., & Winkler, G. S. (2023). Structure and function of molecular machines involved in deadenylation-dependent 5′-3′ mRNA degradation. Frontiers in Genetics, 14, Article 1233842. https://doi.org/10.3389/fgene.2023.1233842

In eukaryotic cells, the synthesis, processing, and degradation of mRNA are important processes required for the accurate execution of gene expression programmes. Fully processed cytoplasmic mRNA is characterised by the presence of a 5′cap structure... Read More about Structure and function of molecular machines involved in deadenylation-dependent 5′-3′ mRNA degradation.

Disruption of the Mammalian Ccr4–Not Complex Contributes to Transcription-Mediated Genome Instability (2023)
Journal Article
Hagkarim, N. C., Hajkarim, M. C., Suzuki, T., Fujiwara, T., Winkler, G. S., Stewart, G. S., & Grand, R. J. (2023). Disruption of the Mammalian Ccr4–Not Complex Contributes to Transcription-Mediated Genome Instability. Cells, 12(14), Article 1868. https://doi.org/10.3390/cells12141868

The mammalian Ccr4–Not complex, carbon catabolite repression 4 (Ccr4)-negative on TATA-less (Not), is a large, highly conserved, multifunctional assembly of proteins that acts at different cellular levels to regulate gene expression. It is involved i... Read More about Disruption of the Mammalian Ccr4–Not Complex Contributes to Transcription-Mediated Genome Instability.

Regulation of eukaryotic mRNA deadenylation and degradation by the Ccr4-Not complex (2023)
Journal Article
Pavanello, L., Hall, M., & Winkler, G. S. (2023). Regulation of eukaryotic mRNA deadenylation and degradation by the Ccr4-Not complex. Frontiers in Cell and Developmental Biology, 11, Article 1153624. https://doi.org/10.3389/fcell.2023.1153624

Accurate and precise regulation of gene expression programmes in eukaryotes involves the coordinated control of transcription, mRNA stability and translation. In recent years, significant progress has been made about the role of sequence elements in... Read More about Regulation of eukaryotic mRNA deadenylation and degradation by the Ccr4-Not complex.

Structural Model of the Human BTG2–PABPC1 Complex by Combining Mutagenesis, NMR Chemical Shift Perturbation Data and Molecular Docking (2022)
Journal Article
Ameerul, A., Almasmoum, H., Pavanello, L., Dominguez, C., & Winkler, G. S. (2022). Structural Model of the Human BTG2–PABPC1 Complex by Combining Mutagenesis, NMR Chemical Shift Perturbation Data and Molecular Docking. Journal of Molecular Biology, 434(14), Article 167662. https://doi.org/10.1016/j.jmb.2022.167662

Degradation of cytoplasmic mRNA in eukaryotes involves the shortening and removal of the mRNA poly(A) tail by poly(A)-selective ribonuclease (deadenylase) enzymes. In human cells, BTG2 can stimulate deadenylation of poly(A) bound by cytoplasmic poly(... Read More about Structural Model of the Human BTG2–PABPC1 Complex by Combining Mutagenesis, NMR Chemical Shift Perturbation Data and Molecular Docking.

Structure of the human Ccr4-Not nuclease module using X-ray crystallography and electron paramagnetic resonance spectroscopy distance measurements (2021)
Journal Article
Zhang, Q., Pavanello, L., Potapov, A., Bartlam, M., & Winkler, G. S. (2022). Structure of the human Ccr4-Not nuclease module using X-ray crystallography and electron paramagnetic resonance spectroscopy distance measurements. Protein Science, 31(3), 758-764. https://doi.org/10.1002/pro.4262

Regulated degradation of mature, cytoplasmic mRNA is a key step in eukaryotic gene regulation. This process is typically initiated by the recruitment of deadenylase enzymes by cis-acting elements in the 3' untranslated region resulting in the shorten... Read More about Structure of the human Ccr4-Not nuclease module using X-ray crystallography and electron paramagnetic resonance spectroscopy distance measurements.

Design of artificial metalloenzymes for the reduction of nicotinamide cofactors (2021)
Journal Article
Basle, M., Padley, H. A., Martins, F. L., Winkler, G. S., Jäger, C. M., & Pordea, A. (2021). Design of artificial metalloenzymes for the reduction of nicotinamide cofactors. Journal of Inorganic Biochemistry, 220, Article 111446. https://doi.org/10.1016/j.jinorgbio.2021.111446

Artificial metalloenzymes result from the insertion of a catalytically active metal complex into a biological scaffold, generally a protein devoid of other catalytic functionalities. As such, their design requires efforts to engineer substrate bindin... Read More about Design of artificial metalloenzymes for the reduction of nicotinamide cofactors.

Structural and binding characterization of the LacdiNAc-specific adhesin (LabA; HopD) exodomain from Helicobacter pylori (2020)
Journal Article
Paraskevopoulou, V., Schimpl, M., Overman, R. C., Stolnik, S., Chen, Y., Nguyen, L., …Falcone, F. H. (2021). Structural and binding characterization of the LacdiNAc-specific adhesin (LabA; HopD) exodomain from Helicobacter pylori. Current Research in Structural Biology, 3, 19-29. https://doi.org/10.1016/j.crstbi.2020.12.004

Helicobacter pylori (H. pylori) uses several outer membrane proteins for adhering to its host's gastric mucosa, an important step in establishing and preserving colonization. Several adhesins (SabA, BabA, HopQ) have been characterized in terms of the... Read More about Structural and binding characterization of the LacdiNAc-specific adhesin (LabA; HopD) exodomain from Helicobacter pylori.

Frequent loss of BTG1 activity and impaired interactions with the Caf1 subunit of the Ccr4–Not deadenylase in non-Hodgkin lymphoma (2020)
Journal Article
Almasmoum, H., Airhihen, B., Seedhouse, C., & Winkler, G. S. (2020). Frequent loss of BTG1 activity and impaired interactions with the Caf1 subunit of the Ccr4–Not deadenylase in non-Hodgkin lymphoma. Leukemia & Lymphoma, 62(2), 281-290. https://doi.org/10.1080/10428194.2020.1827243

© 2020 Informa UK Limited, trading as Taylor & Francis Group. Mutations in the highly similar genes B-cell translocation gene 1 (BTG1) and BTG2 are identified in approximately 10–15% of non-Hodgkin lymphoma cases, which may suggest a direct involve... Read More about Frequent loss of BTG1 activity and impaired interactions with the Caf1 subunit of the Ccr4–Not deadenylase in non-Hodgkin lymphoma.

Introduction of a C-terminal hexa-lysine tag increases thermal stability of the LacDiNac binding adhesin (LabA) exodomain from Helicobacter pylori (2019)
Journal Article
Paraskevopoulou, V., Artiaga, V. G., Rowlinson, R., Winkler, G. S., Gellert, P., Stolnik, S., …Falcone, F. H. (2019). Introduction of a C-terminal hexa-lysine tag increases thermal stability of the LacDiNac binding adhesin (LabA) exodomain from Helicobacter pylori. Protein Expression and Purification, 163, 1-8. https://doi.org/10.1016/j.pep.2019.105446

Helicobacter pylori is a pathogenic microorganism infecting approximately 50% of the global population, and establishes life-long colonization despite the hostile stomach environment. H. pylori employs a wide range of outer membrane proteins (adhesin... Read More about Introduction of a C-terminal hexa-lysine tag increases thermal stability of the LacDiNac binding adhesin (LabA) exodomain from Helicobacter pylori.

The central region of CNOT1 and CNOT9 stimulate deadenylation by the Ccr4 Not nuclease module (2018)
Journal Article
Pavanello, L., Hall, B., Airhihen, B., & Winkler, G. S. (2018). The central region of CNOT1 and CNOT9 stimulate deadenylation by the Ccr4 Not nuclease module. Biochemical Journal, 475(21), 3437–3450. https://doi.org/10.1042/bcj20180456

Regulated degradation of cytoplasmic mRNA is important for the accurate execution of gene expression programmes in eukaryotic cells. A key step in this process is the shortening and removal of the mRNA poly(A) tail, which can be achieved by the recru... Read More about The central region of CNOT1 and CNOT9 stimulate deadenylation by the Ccr4 Not nuclease module.

Post-transcriptional control of tumor cell autonomous metastatic potential by the CCR4-NOT deadenylase CNOT7 (2016)
Journal Article
Faraji, F., Hu, Y., Yang, H. H., Lee, M. P., Winkler, G. S., Hafner, M., & Hunter, K. W. (2016). Post-transcriptional control of tumor cell autonomous metastatic potential by the CCR4-NOT deadenylase CNOT7. PLoS Genetics, 12, Article e1005820. https://doi.org/10.1371/journal.pgen.1005820

Accumulating evidence supports the role of an aberrant transcriptome as a driver of metastatic potential. Deadenylation is a general regulatory node for post-transcriptional control by microRNAs and other determinants of RNA stability. Previously, we... Read More about Post-transcriptional control of tumor cell autonomous metastatic potential by the CCR4-NOT deadenylase CNOT7.

A non-proteolytic role for ubiquitin in deadenylation by the RNA-binding E3 ligase MEX-3C (2015)
Journal Article
Cano, F., Rapiteanu, R., Winkler, G., & Lehner, P. J. (2015). A non-proteolytic role for ubiquitin in deadenylation by the RNA-binding E3 ligase MEX-3C. Nature Communications, 6, Article 8670. https://doi.org/10.1038/ncomms9670

The regulation of protein and mRNA turnover is essential for many cellular processes. We recently showed that ubiquitin—traditionally linked to protein degradation—directly regulates the degradation of mRNAs through the action of a newly identified f... Read More about A non-proteolytic role for ubiquitin in deadenylation by the RNA-binding E3 ligase MEX-3C.

Structural basis of Lewis(b) antigen binding by the Helicobacter pylori adhesin BabA (2015)
Journal Article
Hage, N., Howard, T., Phillips, C., Brassington, C., Overman, R., Debreczeni, J., …Falcone, F. H. (2015). Structural basis of Lewis(b) antigen binding by the Helicobacter pylori adhesin BabA. Science Advances, 1(7), Article e1500315. https://doi.org/10.1126/sciadv.1500315

Helicobacter pylori is a leading cause of peptic ulceration and gastric cancer worldwide. To achieve colonization of the stomach, this Gram-negative bacterium adheres to Lewis(b) (Le(b)) antigens in the gastric mucosa using its outer membrane protein... Read More about Structural basis of Lewis(b) antigen binding by the Helicobacter pylori adhesin BabA.

Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1 (2015)
Journal Article

Eukaryotic mRNA contains a 3? poly(A) tail, which plays important roles in the regulation of mRNA stability and translation. Well-characterized enzymes involved in the shortening of the poly(A) tail include the multi-subunit Ccr4-Not deadenylase, whi... Read More about Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1.

The enzyme activities of Caf1 and Ccr4 are both required for deadenylation by the human Ccr4-Not nuclease module (2015)
Journal Article
Maryati, M., Airhihen, B., & Winkler, G. S. (2015). The enzyme activities of Caf1 and Ccr4 are both required for deadenylation by the human Ccr4-Not nuclease module. Biochemical Journal, 469(1), https://doi.org/10.1042/BJ20150304

In eukaryotic cells, the shortening and removal of the poly(A) tail (deadenylation) of cytoplasmic mRNA is a key event in regulated mRNA degradation. A major enzyme involved in deadenylation is the Ccr4-Not deadenylase complex, which can be recruited... Read More about The enzyme activities of Caf1 and Ccr4 are both required for deadenylation by the human Ccr4-Not nuclease module.

Improved expression and purification of the Helicobacter pylori adhesin BabA through the incorporation of a hexa-lysine tag (2014)
Journal Article

Helicobacter pylori is a pathogenic bacterium that has the remarkable ability to withstand the harsh conditions of the stomach for decades. This is achieved through unique evolutionary adaptations, which include binding Lewisb antigens found on the g... Read More about Improved expression and purification of the Helicobacter pylori adhesin BabA through the incorporation of a hexa-lysine tag.