Nature
Basic Forestry and Proteomics Research Centre, Haixia Institute of Science and Technology, Fujian Agriculture and Forestry University, Fuzhou, P. R. China.
Published: March 2021
The evolutionarily conserved target of rapamycin (TOR) kinase acts as a master regulator that coordinates cell proliferation and growth by integrating nutrient, energy, hormone and stress signals in all eukaryotes. Research has focused mainly on TOR-regulated translation, but how TOR orchestrates the global transcriptional network remains unclear. Here we identify ethylene-insensitive protein 2 (EIN2), a central integrator that shuttles between the cytoplasm and the nucleus, as a direct substrate of TOR in Arabidopsis thaliana. Glucose-activated TOR kinase directly phosphorylates EIN2 to prevent its nuclear localization. Notably, the rapid global transcriptional reprogramming that is directed by glucose-TOR signalling is largely compromised in the ein2-5 mutant, and EIN2 negatively regulates the expression of a wide range of target genes of glucose-activated TOR that are involved in DNA replication, cell wall and lipid synthesis and various secondary metabolic pathways. Chemical, cellular and genetic analyses reveal that cell elongation and proliferation processes that are controlled by the glucose-TOR-EIN2 axis are decoupled from canonical ethylene-CTR1-EIN2 signalling, and mediated by different phosphorylation sites. Our findings reveal a molecular mechanism by which a central signalling hub is shared but differentially modulated by diverse signalling pathways using distinct phosphorylation codes that can be specified by upstream protein kinases.
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http://dx.doi.org/10.1038/s41586-021-03310-y | DOI Listing |
PLoS One
January 2025
Center of Gene Sequencing, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, P. R. China.
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January 2025
Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
Historically, plant derived natural products and their crude extracts have been used to treat a wide range of ailments across the world. Biogerontology research aims to explore the molecular basis of aging and discover new anti-aging therapeutic compounds or formulations to combat the detrimental effects of aging and promote a healthy life span. The budding yeast has been, and continues to be, an indispensable model organism in the field of biomedical research for discovering the molecular basis of aging has preserved nutritional signaling pathways (such as the target of rapamycin (TOR)-Sch9 and the Ras-AC-PKA (cAMP-dependent protein kinase) pathways, and shows two distinct aging paradigms chronological life span (CLS) and replicative life span (RLS).
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Dipartimento Di Ricerca Traslazionale E Delle Nuove Tecnologie in Medicina E Chirurgia, Università Di Pisa, Via Savi 10, 56126, Pisa, Italy.
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Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Myeloid malignancies are heterogenous disorders characterized by distinct molecular drivers but share convergence of oncogenic signaling pathways and propagation by ripe pro-inflammatory niches. Here, we establish a comprehensive transcriptional atlas across the spectrum of myeloproliferative neoplasms (MPN) and secondary acute myeloid leukemia (sAML) through RNA-sequencing of 158 primary samples encompassing CD34+ hematopoietic stem/progenitor cells and CD14+ monocytes. Supported by mass cytometry (CyTOF) profiling, we reveal aberrant networks of PI3K/AKT/mTOR signalling and NFκB-mediated hyper-inflammation.
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January 2025
Department of Obstetrics and Gynecology, Shiga University of Medical Science, 520-2192/Seta Tsukinowa-cho, Otsu, Shiga, Japan.
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