IndraLab

Statements



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"To test whether USP28 activity is sufficient for senescence induction, USP28 was overexpressed and found to induce senescence (as indicated by growth arrest and positive SA-β-Gal staining) (Fig. 3A,B; Supplemental Fig. S3I,J) comparable with p21 overexpression."

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"USP28 overexpression increased the levels of multiple senescence markers, including p53, p21 , and GATA4 proteins but not p16, again suggesting that USP28 may be inducing senescence in part through the p53 and GATA4 branches (Fig. 3C–E; Supplemental Fig. S3K,L)."

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"To determine the dependency of p53 and GATA4 in USP28-induced senescence, we combined doxycycline-inducible (Tet-on) USP28 overexpression with either p53 inhibition (via E6 expression) or GATA4 depletion in BJ fibroblasts."

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"E6 or GATA4 depletion blunted USP28-induced senescence (Supplemental Fig. S4A)."

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"While either p53 or GATA4 depletion via shRNA reduced USP28-induced senescence as measured by SA-β-Gal activity, codepletion of p53 and GATA4 resulted in a synergistic effect (Fig. 3D)."

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"Together, these results indicate that p53 and GATA4 each independently contributes to USP28-induced senescence."