IndraLab

Statements

USP46 is phosphorylated. 15 / 15
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"As the phosphorylation of USP46 is poorly studied, the protein kinases other than CK1δ responsible for the basic phosphorylation of USP46 need further investigation in the future."
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"CK1δ-mediated phosphorylation of USP46 in the in vitro kinase assay was detected by using phospho-tag gel, which was significantly mitigated by the treatment of PF670462 (Fig. xref )."
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"The single mutation of USP46 T209A, S351A or S354A only mildly decreased the phosphorylation of USP46, while the 3A mutant (T209A/S351A/S354A) almost completely abolished it assessed by phospho-tag gel (Fig. xref )."
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"Mechanistically, CK1δ directly phosphorylates USP46 and activates its deubiquitinase activity towards NRAS mutants, thus promoting oncogenic NRAS-driven melanocyte malignant transformation and melanoma progression in vitro and in vivo."
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"Furthermore, the in vitro kinase assay was performed by using anti-p-Ser and anti-p-Thr antibodies to examine the phosphorylation of USP46 isolated from SK-MEL-103 cells stably expressing pLVX3-GST-USP46 WT and the 3A mutant."
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"Mechanistically, CK1δ directly phosphorylates and activates USP46, thereby promoting oncogenic NRAS-driven melanocyte transformation and tumor progression."
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"As shown in Supplementary Fig.  xref , CK1δ significantly increased the phosphorylation of USP46 WT assessed by anti-p-Ser and anti-p-Thr antibodies, whereas the 3A mutant could largely decrease such phosphorylation events."
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"Intriguingly, some basal phosphorylation of isolated USP46 from SK-MEL-103 cells was noticed even in the absence of CK1δ, indicating that other protein kinases might also contribute to the phosphorylation of USP46."
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"CK1δ-mediated phosphorylation of USP46 regulates tumor progression of oncogenic NRAS-driven melanoma."
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"Next, we examined the effect of CK1δ-mediated phosphorylation of USP46 on the ubiquitination of NRAS mutants."
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"We next investigated the function of CK1δ-mediated phosphorylation of USP46 on oncogenic NRAS-dependent malignant processes."
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"These results indicate that CK1δ-mediated phosphorylation of USP46 is pivotal to stabilize NRAS mutant and promote oncogenic NRAS-dependent tumor progression."
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"Mechanistically, CK1δ-mediated phosphorylation of USP46 is a critical post-translational mechanism that controls stability and oncogenic function of these NRAS mutants."
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"Second, CK1δ binds and regulates the phosphorylation of USP46 (Fig. xref and Supplementary Fig.  xref )."
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"Interestingly, we did notice some basal phosphorylation of isolated USP46 from SK-MEL-103 cells even in the absence of CK1δ (Supplementary Fig.  xref ), indicating that other protein kinases might also contribute to the phosphorylation of USP46."
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