Cited by 414Cancer-related Molecular PathwaysHeat shock proteins researchUbiquitin and proteasome pathways

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p300/MDM2 Complexes Participate in MDM2-Mediated p53 Degradation

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Grossman, Steven R, Perez, Marco, Kung, Andrew L, Joseph, Michael, Mansur, Claire, Xiao, Zhi-Xiong, Kumar, Sushant, Howley, Peter M, Livingston, David M·1998·Molecular Cell

DOI 10.1016/s1097-2765(00)80140-9

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Abstract

Control of p53 turnover is critical to p53 function. E1A binding to p300/CBP translates into enhanced p53 stability, implying that these coactivator proteins normally operate in p53 turnover control. In this regard, the p300 C/H1 region serves as a specific in vivo binding site for both p53 and MDM2, a naturally occurring p53 destabilizer. Moreover, most of the endogenous MDM2 is bound to p300, and genetic analysis implies that specific interactions of p53 and MDM2 with p300 C/H1 are important steps in the MDM2-directed turnover of p53. A specific role for p300 in endogenous p53 degradation is underscored by the p53-stabilizing effect of overproducing the p300 C/H1 domain. Taken together, the data indicate that specific interactions between p300/CBP C/H1, p53, and MDM2 are intimately involved in the MDM2-mediated control of p53 abundance.

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Authors: Grossman, S. R., Perez, M., Kung, A. L., Joseph, M., Mansur, C., Xiao, Z.-X., Kumar, S., Howley, P. M., & Livingston, D. M.
Affiliations: Harvard University (US)
Tufts University (US)
Boston University (US)
Corresponding author: Livingston, David M
ORCID: Grossman, Steven R
Perez, Marco
Kung, Andrew L
Joseph, Michael
Xiao, Zhi-Xiong
Kumar, Sushant
Howley, Peter M
Livingston, David M
Venue: Molecular Cell
Publisher: Elsevier BV
Published: 1998-10
Volume: 2
Issue: 4
Pages: 405-415
ISSN: 1097-2765 (ISSN-L)
DOI: 10.1016/s1097-2765(00)80140-9
OpenAlex: W2063877452
Cited by: 414
References: 63
Citations by year: 2026: 2 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 7 · 2021: 4 · 2020: 9 · 2019: 4 · 2018: 6 · 2017: 2 · 2016: 9 · 2015: 4 · 2014: 15 · 2013: 15 · 2012: 18
FWCI: 19.07
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor, 923 d)
Locations: Molecular Cell (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords: P300, MDM2, p53 degradation, CBP, adenovirus E1A, protein-protein interaction, p53 stabilization, tumor suppressor regulation
MeSH terms: Cell Line, DNA-Binding Proteins, Humans, Molecular Sequence Data, Neoplasm Proteins, Nuclear Proteins, Oncogene Proteins, Viral, Protein Binding, Proto-Oncogene Proteins, Ubiquitins, Trans-Activators, Tumor Suppressor Protein p53, Mutagenesis, Sequence Homology, Amino Acid, Proto-Oncogene Proteins c-mdm2

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p300/MDM2 Complexes Participate in MDM2-Mediated p53 Degradation

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