Linked Life Data

21706477

Source:http://linkedlifedata.com/resource/pubmed/id/21706477

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-9-7
pubmed:abstractText
By activating protective pathways, tumour cells are not only capable of survival in stress, but often associated with increased aggressiveness and metastasis. Activating transcription factor 4 (ATF4) is a major coordinator of tumour cell survival in stress and is commonly overexpressed in tumours. Numerous studies suggested that the ATF4 is a potential therapeutic target for cancer. In this report, we describe that a small ribosomal peptide, RPL41, induced rapid ATF4 degradation. By immunofluorescence staining, RPL41 induced ATF4 relocation from nuclei to cytoplasm, where ATF4 co-stained with a proteasome marker; the RPL41-induced ATF4 relocation and degradation were blocked by the proteasome inhibitor MG132. An in vivo phosphorylation study showed that RPL41 induced ATF4 phosphorylation and serine 219 of ATF4 was essential for RPL41-induced ATF4 degradation. Cells with RPL41 knockdown had significantly increased ATF4, suggesting that RPL41 could play a physiological role in regulating the cellular ATF4 level. RPL41 was capable of inducing tumour cell death and cell cycle arrest; at low dose, RPL41 sensitized tumour cells A549 to the DNA damage agent cisplatin. These studies suggest that RPL41, a small peptide that is chemically synthesizable and capable of self-cell penetration, may have potential as an anti-ATF4 agent for cancer therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1096-9896
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
pubmed:issnType
Electronic
pubmed:volume
225
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
285-92
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Ribosomal protein RPL41 induces rapid degradation of ATF4, a transcription factor critical for tumour cell survival in stress.
pubmed:affiliation
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article