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• W2300552754 abstract "TRIB2, a serine/threonine pseudokinase identified as an oncogene, is expressed at high levels in the T-cell compartment of hematopoiesis. The proliferation of developing thymocytes is tightly controlled to prevent leukemic transformation of T cells. Here we examine Trib2 loss in murine hematopoiesis under steady state and proliferative stress conditions, including genotoxic and oncogenic stress. Trib2 (-/-) developing thymocytes show increased proliferation, and Trib2 (-/-) mice have significantly higher thymic cellularity at steady state. During stress hematopoiesis, Trib2 (-/-) developing thymocytes undergo accelerated proliferation and demonstrate hypersensitivity to 5-fluorouracil (5-FU)-induced cell death. Despite the increased cell death post 5-FU-induced proliferative stress, Trib2 (-/-) mice exhibit accelerated thymopoietic recovery post treatment due to increased cell division kinetics of developing thymocytes. The increased proliferation in Trib2 (-/-) thymocytes was exacerbated under oncogenic stress. In an experimental murine T-cell acute lymphoblastic leukemia (T-ALL) model, Trib2 (-/-) mice had reduced latency in vivo, which associated with impaired MAP kinase (MAPK) activation. High and low expression levels of Trib2 correlate with immature and mature subtypes of human T-ALL, respectively, and associate with MAPK. Thus, TRIB2 emerges as a novel regulator of thymocyte cellular proliferation, important for the thymopoietic response to genotoxic and oncogenic stress, and possessing tumor suppressor function." @default.
• W2300552754 created "2016-06-24" @default.
• W2300552754 creator A5003981842 @default.
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• W2300552754 creator A5066567943 @default.
• W2300552754 date "2016-03-15" @default.
• W2300552754 modified "2023-10-12" @default.
• W2300552754 title "TRIB2 regulates normal and stress-induced thymocyte proliferation" @default.
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• W2300552754 doi "https://doi.org/10.1038/celldisc.2015.50" @default.
• W2300552754 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4860960" @default.
• W2300552754 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27462446" @default.
• W2300552754 hasPublicationYear "2016" @default.
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