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Statements


CYLD deubiquitinates TP53. 9 / 9
1 | 8

"Mechanistically, CYLD interacts with and deubiquitinates p53 facilitating its stabilization in response to genotoxic stress.| Collectively, our results identify CYLD as a deubiquitinase facilitating DNA damage-induced p53 activation and suggest that regulation of p53 responses to genotoxic stress contributes to the tumour suppressor function of CYLD."

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"As shown in XREF_FIG and XREF_SUPPLEMENTARY, in contrast to WT CYLD, the catalytically inactive CYLDR936X (R/X) and CYLDH871N (H/N) mutants did not diminish p53 ubiquitination although they bound p53, demonstrating that CYLD DUB activity is required to reduce p53 ubiquitination."

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"To address this question, we first assessed the capacity of CYLD to reduce p53 ubiquitination in cells overexpressing HA tagged Lys-to-Arg ubiquitin mutants that can only form K48- or K63 linked chains."

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"Furthermore, recombinant His CYLD reduced ubiquitination of Flag-p53 immunoprecipitated from CpT treated HEK293T cells, showing that CYLD can directly deubiquitinate p53 in a cell-free in vitro assay (XREF_SUPPLEMENTARY)."

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"CYLD deubiquitinates p53 facilitating its stabilization."

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"Together, these results suggested that CYLD directly interacts with and deubiquitinates p53 facilitating its optimal stabilization in response to DNA damage."

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"Mechanistically, we show that CYLD interacts with and deubiquitinates p53 in response to DNA damage."

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"This experiment showed that CYLD diminishes p53 ubiquitination in cells expressing HA-mutant ubiquitin forming K63 only chains, but also in cells expressing HA-mutant ubiquitin forming K48 only chains (XREF_FIG)."

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"Mechanistically, CYLD interacts with and deubiquitinates p53 facilitating its stabilization in response to genotoxic stress."