rdf:type |
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lifeskim:mentions |
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pubmed:issue |
26
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pubmed:dateCreated |
2011-6-27
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pubmed:abstractText |
Ribosomal proteins play a critical role in tightly coordinating p53 signaling with ribosomal biogenesis. Several ribosomal proteins have been shown to induce and activate p53 via inhibition of MDM2. Here, we report that S27a, a small subunit ribosomal protein synthesized as an 80-amino acid ubiquitin C-terminal extension protein (CEP80), functions as a novel regulator of the MDM2-p53 loop. S27a interacts with MDM2 at the central acidic domain of MDM2 and suppresses MDM2-mediated p53 ubiquitination, leading to p53 activation and cell cycle arrest. Knockdown of S27a significantly attenuates the p53 activation in cells in response to treatment with ribosomal stress-inducing agent actinomycin D or 5-fluorouracil. Interestingly, MDM2 in turn ubiquitinates S27a and promotes proteasomal degradation of S27a in response to actinomycin D treatment, thus forming a mutual-regulatory loop. Altogether, our results reveal that S27a plays a non-redundant role in mediating p53 activation in response to ribosomal stress via interplaying with MDM2.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin,
http://linkedlifedata.com/resource/pubmed/chemical/MAML2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleic Acid Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TP53 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitins,
http://linkedlifedata.com/resource/pubmed/chemical/ribosomal protein S27a,
http://linkedlifedata.com/resource/pubmed/chemical/ubiquitin precursor
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1083-351X
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
286
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
22730-41
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pubmed:meshHeading |
pubmed-meshheading:21561866-Cell Cycle,
pubmed-meshheading:21561866-DNA-Binding Proteins,
pubmed-meshheading:21561866-Dactinomycin,
pubmed-meshheading:21561866-Gene Knockdown Techniques,
pubmed-meshheading:21561866-HeLa Cells,
pubmed-meshheading:21561866-Humans,
pubmed-meshheading:21561866-Nuclear Proteins,
pubmed-meshheading:21561866-Nucleic Acid Synthesis Inhibitors,
pubmed-meshheading:21561866-Proteasome Endopeptidase Complex,
pubmed-meshheading:21561866-Protein Precursors,
pubmed-meshheading:21561866-Protein Structure, Tertiary,
pubmed-meshheading:21561866-Ribosomal Proteins,
pubmed-meshheading:21561866-Signal Transduction,
pubmed-meshheading:21561866-Stress, Physiological,
pubmed-meshheading:21561866-Transcription Factors,
pubmed-meshheading:21561866-Tumor Suppressor Protein p53,
pubmed-meshheading:21561866-Ubiquitination,
pubmed-meshheading:21561866-Ubiquitins
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pubmed:year |
2011
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pubmed:articleTitle |
Interplay between ribosomal protein S27a and MDM2 protein in p53 activation in response to ribosomal stress.
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pubmed:affiliation |
Department of Molecular and Medical Genetics, School of Medicine and the OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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