Cited by 244Drug Transport and Resistance MechanismsCancer-related Molecular PathwaysPharmacogenetics and Drug Metabolism

Mutant p53 Cooperates with ETS and Selectively Up-regulates Human MDR1 Not MRP1

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Sampath, Janardhan, Sun, Daxi, Kidd, Vincent J., Grenet, Jose, Gandhi, Amisha, Shapiro, Linda H., Wang, Qingjian, Zambetti, Gerard P. +1 more·2001·Journal of Biological Chemistry

Abstract

The most frequently expressed drug resistance genes, MDR1 and MRP1, occur in human tumors with mutant p53. However, it was unknown if mutant p53 transcriptionally regulated both MDR1 and MRP1. We demonstrated that mutant p53 did not activate either the MRP1 promoter or the endogenous gene. In contrast, mutant p53 strongly up-regulated the MDR1 promoter and expression of the endogenous MDR1 gene. Notably, cells that expressed either a transcriptionally inactive mutant p53 or the empty vector showed no endogenous MDR1 up-regulation. Transcriptional activation of the MDR1 promoter by mutant p53 required an Ets binding site, and mutant p53 and Ets-1 synergistically activated MDR1 transcription. Biochemical analysis revealed that Ets-1 interacted exclusively with mutant p53s in vivo but not with wild-type p53. These findings are the first to demonstrate the induction of endogenous MDR1 by mutant p53 and provide insight into the mechanism.

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Crossref · 10.1074/jbc.m103429200

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  • GOF mut-p53 exhibits interactions with distinct transcription factors (e.g., NF-ɣ, SREBP, VDR, Sp1, ETS2, NFR2, p73, p63) that promote tumor initiation and progression.

    “In contrast to wt-p53, GOF mut-p53 exhibits interactions with distinct transcription factors (e.g., NF-ɣ, SREBP, VDR, Sp1, ETS2, NFR2, p73, p63) that promote tumor initiation and progression [13,72,73,74,75,76,77].”

    From The p53 Pathway in Glioblastoma (2018) · cites this paper as [76]

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Authors
Sampath, J., Sun, D., Kidd, V. J., Grenet, J., Gandhi, A., Shapiro, L. H., Wang, Q., Zambetti, G. P., & Schuetz, J. D.
Affiliations
St. Jude Children's Research Hospital (US)
Corresponding author
Schuetz, John D.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2001-10
Volume
276
Issue
42
Pages
39359-39367
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2050569275
Cited by
244
References
42
Citations by year
2026: 1 · 2025: 5 · 2024: 14 · 2023: 8 · 2022: 8 · 2021: 10 · 2020: 9 · 2019: 5 · 2018: 13 · 2017: 13 · 2016: 8 · 2015: 14 · 2014: 19 · 2013: 5 · 2012: 16
FWCI
4.14
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Heart, Lung, and Blood Institute (P01HL070694)
  • National Cancer Institute (CA-23099, CA63203, P01CA023099, P 30CA 21765, P30CA021765)
  • National Institute of Environmental Health Sciences (ES05851)
Topics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
mutant p53, ETS1, MDR1, MRP1, multidrug resistance, transcriptional activation, Ets binding site, protein-protein interaction, drug resistance genes, transcriptional cooperation
MeSH terms
Base Sequence, Binding Sites, Cell Line, DNA, Flow Cytometry, Genetic Vectors, Glutathione Transferase, Humans, Luciferases, Molecular Sequence Data, Mutation, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Proteins, Ribonucleases, Transcription Factors, Transcription, Genetic, Protein Biosynthesis, Tumor Cells, Cultured, Blotting, Western, Transcriptional Activation, Up-Regulation, Genes, p53, Tumor Suppressor Protein p53, Genes, MDR, ATP Binding Cassette Transporter, Subfamily B, Member 1, Caspases, ATP-Binding Cassette, Sub-Family C Proteins, Multidrug Resistance-Associated Proteins, Proto-Oncogene Proteins c-ets, Proto-Oncogene Protein c-ets-1

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