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Our findings demonstrate that inhibition of PIN1- and CDK4 cooperatively and irreversibly reactivates APC/C CDH1 to induce robust degradation of PIN1 and other mitotic proteins, suggesting potential synergistic effects of combining the PIN1 inhibitors with the CDK4 inhibitors to facilitate the efficacy of PIN1 inhibitors or CDK4 inhibitors in TNBC, especially in RB -deficient tumors

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It cannot be ruled out that OTUD5 may also cleave K48 linkages modified on TRAF2 or on other substrates

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