Document Detail

Ribosomal protein RPL41 induces rapid degradation of ATF4, a transcription factor critical for tumour cell survival in stress.
MedLine Citation:
PMID:  21706477     Owner:  NLM     Status:  Publisher    
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. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Aiyuan Wang; Shengqiang Xu; Xiaoxian Zhang; Jie He; Donghui Yan; Zhangmin Yang; Sheng Xiao
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-18
Journal Detail:
Title:  The Journal of pathology     Volume:  -     ISSN:  1096-9896     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-6-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA; Department of Ophthalmology, Shengjing Hospital, China Medical University, Shenyang City, Liaoning Province, China.
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