p53 x 53BP1

Last update 08 May 2025

Basic Info

Related Targets

p5353BP1

100 Clinical Results associated with p53 x 53BP1

100 Translational Medicine associated with p53 x 53BP1

0 Patents (Medical) associated with p53 x 53BP1

333

Literatures (Medical) associated with p53 x 53BP1

01 May 2025·Chemico-Biological Interactions

Small molecule as potent hepatocellular carcinoma progression inhibitor through stabilizing G-quadruplex DNA to activate replication stress responded DNA damage

Article

Author: Huang, Fei ; He, Dongqing ; Mei, Wenjie ; Wu, Qiong ; Liu, Yan ; Zhao, Bin ; Zeng, Yongchang ; Huang, Jinhua

G-quadruplex (G4) DNA, prevalent in tumor cells, offers a potential anticancer target. This study examined TA-1, a tanshinone IIA derivative, for its antitumor activity against liver cancer. We found that TA-1 binds and stabilizes multiple G4 DNA,triggering DNA damage, suppressing the angiogenesis in vitro and in vivo and leading to cancer cell death. Notably, we confirmed TA-1's inhibitory effect on liver cancer cells and explored its mechanism, which involves stabilizing G4 DNA to mediate replication-stress-dependent DNA damage. Furthermore, TA-1 promotes 53BP1 expression, activating toxic NHEJ repair and leading to apoptotic cell death via the ATM-Chk2-p53 pathway. In vivo studies further supported these findings. In summary, TA-1 is a potent VEGF G-quadruplex stabilizer that inhibits liver cancer progression.

01 Apr 2025·Journal of Investigative Dermatology

Selective USP7 inhibition synergizes with MEK1/2 inhibitor to enhance immune responses and potentiate anti-PD-1 therapy in NRAS mutant melanoma

Article

Author: Cai, Weijia ; Zhang, Qingrun ; Su, Liya ; Yang, Qi ; Ran, Sophia ; Wang, Dinghao ; Purwin, Timothy J

Targeted therapy for NRAS mutant melanoma remains an unmet clinical need. We found that inhibiting Ubiquitin Specific Peptidase 7 (USP7) with the selective USP7 inhibitor (USP7i) FT671 inhibited cell proliferation in NRAS mutant melanoma cell lines. In addition, we identified and validated the knockout of TP53BP1, TP53 or CDKN1A conferred resistance to FT671, suggesting the activation of a functional p53 signaling pathway is essential for the efficacy of USP7i. In Nras mutant melanoma isograft models, FT671 treatment delayed tumor growth. Moreover, the combinatorial treatment with FT671 and MEK1/2 inhibitor (MEKi) was synergistic and induced pyroptosis in vitro. In immunocompetent mice, the combined treatment profoundly suppressed tumor growth, prolonged survival and enhanced intratumoral immune cell infiltration, particularly increasing the ratios of CD8⁺ T cells and mature dendritic cells, indicative of activated antitumor immunity. Notably, the triple combination of USP7i, MEKi, and anti-PD-1 antibody resulted in durable tumor regression, with effects persisting beyond 80 days after treatment cessation. These findings establish USP7i+MEKi as a promising strategy for targeting NRAS, an 'undruggable' mutation in melanoma, and provide a strong rationale for the clinical development of USP7i plus MEKi as an adjuvant therapy to enhance anti-PD-1 immunotherapy in NRAS mutant melanoma patients.

04 Mar 2025·International Journal of Radiation Biology

Dose threshold for residual γH2AX, 53BP1, pATM and p-p53 (Ser-15) foci in X-ray irradiated human fibroblasts

Article

Author: Osipov, Andrey ; Osipov, Andreyan N. ; Yashkina, Elizaveta ; Vorobyeva, Natalia ; Ignatov, Maxim ; Belov, Oleg ; Chigasova, Anna ; Fedotov, Yuriy

BACKGROUNDEnumeration of residual DNA repair foci 24 hours or more after exposure to ionizing radiation (IR) is often used to assess the efficiency of DNA double-strand break repair. However, the relationship between the number of residual foci in irradiated cells and the radiation dose is still poorly understood. The aim of this work was to investigate the dose responses for residual DNA repair foci in normal human fibroblasts after X-ray exposure in the absorbed dose range from 0.1 to 5 Gy.MATERIALS AND METHODSFibroblasts were irradiated using a X-ray unit at an absorbed dose rate of 0.2 Gy/min. Irradiated cells were incubated for 0.5, 24, 48 and 72 h. Immunofluorescence visualized γH2AX, 53BP1, pATM and p-p53 (Ser-15) foci were enumerated using DARFI software and by manual scoring. Additionally, clonogenic survival analysis was performed.RESULTSThe data analysis performed with the hockey stick model showed the presence of a dose threshold for the residual foci of all proteins studied. The estimated threshold doses are close to the quasi-threshold dose (Dq = 0.99 ± 0.09 Gy) calculated from the cell survival curve.CONCLUSIONThe excellent agreement between the calculated values of the threshold dose and Dq in irradiated fibroblasts proves that residual foci are sites, where cells are still attempting to repair potentially lethal DNA damage.

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