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Akademický článek

Autor: Jeung-Hoi Ha, Orjola Prela, Darren R. Carpizo, Stewart N. Loh

Publikováno v: Frontiers in Molecular Biosciences, Vol 9 (2022)

A large percentage of transcription factors require zinc to bind DNA. In this review, we discuss what makes p53 unique among zinc-dependent transcription factors. The conformation of p53 is unusually malleable: p53 binds zinc extremely tightly when f

Externí odkaz: https://doaj.org/article/1fbf4fa9b2c742928e4cf2866141f47d

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Akademický článek

Zinc shapes the folding landscape of p53 and establishes a pathway for reactivating structurally diverse cancer mutants

Autor: Adam R Blanden, Xin Yu, Alan J Blayney, Christopher Demas, Jeung-Hoi Ha, Yue Liu, Tracy Withers, Darren R Carpizo, Stewart N Loh

Publikováno v: eLife, Vol 9 (2020)

Missense mutations in the p53 DNA-binding domain (DBD) contribute to half of new cancer cases annually. Here we present a thermodynamic model that quantifies and links the major pathways by which mutations inactivate p53. We find that DBD possesses t

Externí odkaz: https://doaj.org/article/414b92a82c8d4ddc9d7a0884046cf056

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Data from Combinatorial Therapy of Zinc Metallochaperones with Mutant p53 Reactivation and Diminished Copper Binding

Autor: Darren R. Carpizo, S. David Kimball, Stewart N. Loh, David A. Boothman, John Gilleran, Alan J. Blayney, Bing Na, Tracy Withers, Yue Liu, Adam R. Blanden, Anthony F. Bencivenga, Xin Yu, Saif Zaman

Chemotherapy and radiation are more effective in wild-type (WT) p53 tumors due to p53 activation. This is one rationale for developing drugs that reactivate mutant p53 to synergize with chemotherapy and radiation. Zinc metallochaperones (ZMC) are a n

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::3f7642d9fa72789f4efa9791f6cf5f6b
https://doi.org/10.1158/1535-7163.c.6538219.v1

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Supplementary Tables S1-S5 from Combinatorial Therapy of Zinc Metallochaperones with Mutant p53 Reactivation and Diminished Copper Binding

Supplementary tables to show combination index values for combination treatments of indicated compounds. Supplementary Table 1. Combination Index values for initial combination treatment of ZMC1 with chemotherapy drugs; Supplementary Table 2. Combina

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7b552ac3dcc2e7479c6659a9b74c1df4
https://doi.org/10.1158/1535-7163.22505851.v1

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Supplementary Figures S1-S10 from Combinatorial Therapy of Zinc Metallochaperones with Mutant p53 Reactivation and Diminished Copper Binding

Suppl. Fig. S1 display ZMC1 structure. Suppl. Fig. S2 showed no synergy in combination treatment of ZMC1 and Adriamycin or IR. Suppl. Fig. S3 showed synergy in Detroit 562 cells by combination treatment of ZMC1 and Irinotecan in the presence of GSH.

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::373924276ceb44d0f28384c120bb1228
https://doi.org/10.1158/1535-7163.22505854

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Supplementary methods from Combinatorial Therapy of Zinc Metallochaperones with Mutant p53 Reactivation and Diminished Copper Binding

Suppl. Methods included the methods used in the paper, Cell growth inhibition assay, Immunofluorescent staining, Synthesis of ZMC1, Synthesis of 2,2'-((2-Ethoxy-2-oxoethyl)azanediyl)diacetic acid (NTA-MEE) and NTA-DEE, Zn2+-Kd measurements by competi

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7118ac2756632efdd25988ccd02b669d
https://doi.org/10.1158/1535-7163.22505848.v1

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Data from Zinc Metallochaperones Reactivate Mutant p53 Using an ON/OFF Switch Mechanism: A New Paradigm in Cancer Therapeutics

Autor: Darren R. Carpizo, Stewart N. Loh, S. David Kimball, Chang Chan, Joseph Bertino, Dirk Moore, Brian Buckley, John Gilleran, Hongxia Lin, Tracy Withers, Ashley T. Tsang, Ying Chen, Samuel Kogan, Xin Yu

Purpose: Zinc metallochaperones (ZMC) are a new class of anticancer drugs that reactivate zinc-deficient mutant p53 by raising and buffering intracellular zinc levels sufficiently to restore zinc binding. In vitro pharmacodynamics of ZMCs indicate th

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1e1caa6c09622d14f31a294747889e9b
https://doi.org/10.1158/1078-0432.c.6527462.v1

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Supplementary figures and tables from Zinc Metallochaperones Reactivate Mutant p53 Using an ON/OFF Switch Mechanism: A New Paradigm in Cancer Therapeutics

Supplementary figures and tables Supplementary Fig. S1. Quantitative RT-PCR (qPCR) validation of the expression of MT1A, MT2A, and ZnT1 in TOV112D cells after ZMC1 treatment. Supplementary Fig. S2. Quantitative RT-PCR (qPCR) validation of the knockou

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4704e5d0c18adc372b3f30e43e462a39
https://doi.org/10.1158/1078-0432.22470215.v1

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