IndraLab

Statements

PT33 binds BAP1. 17 / 17
| 11 6
reach
"Here, we described one example of such a mechanism in which PT33 covalently bound BAP1 functions as a molecular linker between BRCA1 and its E3 ligase-HERC2."
37655321
sparser
"We showed that HERC2 can be recruited by the PT33-bound BAP1 and competes with BARD1 to bind to the RING domain of BRCA1, ultimately leading to BRCA1 estrangement from DSB sites."
37655321
reach
"We showed that HERC2 can be recruited by the PT33-bound BAP1 and competes with BARD1 to bind to the RING domain of BRCA1, ultimately leading to BRCA1 estrangement from DSB sites."
37655321
sparser
"On the basis of these findings, we next examined whether the covalently interaction of BAP1 with PT33 may alter BAP1 sub-cellular location, and found that after IR treatment, PT33 had no apparent effect on the nuclear translocation of BAP1 in HCT116 cells ( xref H)."
37655321
reach
"The deubiquitinating activities were calculated as the fluorescence increment (folds) per minute, indicating the deubiquitination rate of substrate Ub-AMC.2.4 Determine the kinetic parameters of covalent binding of PT33 towards BAP1."
37655321
sparser
"These results indicate that PT33 treatment had no apparent impact on the protein level of BRCA1 in presence or absence of BAP1, and suggest that BAP1 inhibition with PT33 (or PT33-bound BAP1) is radically different from BAP1 depletion in HR suppression."
37655321
reach
"We observed that PT33 resulted in the increase of the thermal stability of BAP1, thus confirming that PT33 can bind to BAP1."
37655321
sparser
"BAP1 binding with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction."
37655321
reach
"We then performed molecular docking to predict the binding mode and investigate the PT33–BAP1 interaction interface."
37655321
sparser
"Therefore, we carried out co-IP/WB assays with ectopic expression of Myc- HERC2 (3559–4834 aa 18 ), and found that after IR, PT33-bound BAP1 showed markedly stronger interaction with BRCA1 than uncombined BAP1; only PT33-bound BAP1 could recruit HERC2 to target BRCA1, but not uncombined BAP1."
37655321
reach
"As illustrated in Fig. 4D and Supporting Information Fig. S7A and S7B, PT33 binds to BAP1 catalytic active pocket through several hydrogen bonds."
37655321
reach
"To investigate the possibility of PT33 covalently binding to BAP1, we synthesized a biotinylated affinity probe-PT33–Biotin by modifying the hydroxy of PT33 with biotin (Supporting Information Figs."
37655321
reach
"These results indicate that PT33 treatment had no apparent impact on the protein level of BRCA1 in presence or absence of BAP1, and suggest that BAP1 inhibition with PT33 (or PT33-bound BAP1) is radically different from BAP1 depletion in HR suppression."
37655321
reach
"In brief, these results indicate that PT33 suppresses HR-mediated DSB repair by targeting BAP1 to trigger the accumulation of K48-linked polyubiquitinated BRCA1, which interrupts HR process.3.5 BAP1 binding with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction."
37655321
reach
"Therefore, we carried out co-IP/WB assays with ectopic expression of Myc-HERC2 (3559–4834 aa ), and found that after IR, PT33-bound BAP1 showed markedly stronger interaction with BRCA1 than uncombined BAP1; only PT33-bound BAP1 could recruit HERC2 to target BRCA1, but not uncombined BAP1."
37655321
sparser
"Together, these results demonstrate that PT33-bound BAP1 recruits HERC2 and competes with BARD1 for BRCA1 interaction, suppressing BRCA1-mediated DNA repair."
37655321
reach
"Together, these results demonstrate that PT33-bound BAP1 recruits HERC2 and competes with BARD1 for BRCA1 interaction, suppressing BRCA1-mediated DNA repair.Based on these observations, we noticed that PT33 functions may require cooperation with BAP1 or HERC2."
37655321