Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: SMURF2 phosphorylation at Thr249 modifies the stemness and tumorigenicity of glioma stem cells by regulating TGF-β receptor stability Glioma stem cells (GSCs) contribute to the pathogenesis of glioblastoma, the most malignant form of glioma. The implication and underlying mechanisms of SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) on the GSC phenotypes remain unknown. We previously demonstrated that SMURF2 phosphorylation at Thr249 (SMURF2Thr249) activates its E3 ubiquitin ligase activity. Here, we demonstrate that SMURF2Thr249 phosphorylation plays an essential role in maintaining GSC stemness and tumorigenicity. SMURF2 silencing augmented the self-renewal potential and tumorgenicity of patient-derived GSCs. The SMURF2Thr249 phosphorylation level was low in human glioblastoma pathology specimens. Introduction of the SMURF2T249A mutant resulted in increased stemness and tumorgenicity of GSCs, recapitulating the SMURF2 silencing. Moreover, the inactivation of SMURF2Thr249 phosphorylation increases TGF-{beta} receptor (TGFBR) protein stability. Indeed, TGFBR1 knockdown markedly counteracted the GSC phenotypes by SMURF2T249A mutant. These findings highlight the importance of SMURF2Thr249 phosphorylation in maintaining GSC phenotypes, thereby demonstrating a potential target for GSC-directed therapy.
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The categories of this paper are: neuroscience
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The categories of this paper are: developmental
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The categories of this paper are: evolutionary
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The categories of this paper are: immunology
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The categories of this paper are: cell
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The categories of this paper are: systems
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The categories of this paper are: microbiology
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The categories of this paper are: plant
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The categories of this paper are: biochemistry
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The categories of this paper are: epidemiology
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The categories of this paper are: zoology
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The categories of this paper are: ecology
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The categories of this paper are: communication
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The categories of this paper are: bioengineering
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The categories of this paper are: bioinformatics
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The categories of this paper are: biophysics