Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2011-6-27
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22730-41
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
pubmed:year
2011
pubmed:articleTitle
Interplay between ribosomal protein S27a and MDM2 protein in p53 activation in response to ribosomal stress.
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.
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