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PMID: 18281479 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Nucleolin stabilizes Bcl-X L messenger RNA in response to UVA irradiation.

Cancer research ·Vol. 68 ·No. 4 ·2008-02-15 ·Pages 1046-54

Zhang J, Tsaprailis G, Bowden GT

Abstract

Our laboratory has previously reported that UVA irradiation can increase the expression of Bcl-X(L), an antiapoptotic molecule, by stabilizing its mRNA in cultured immortalized human keratinocytes. To understand the mechanism by which the Bcl-X(L) message is stabilized, we used a synthetic Bcl-X(L) 3'-untranslated region (UTR) to capture RNA-binding proteins. Nucleolin was identified as one of the binding proteins as determined by tandem mass spectrometry coupled to liquid chromatography analysis. Further study showed that nucleolin specifically recognized the AU-rich elements (AUUUA) in the 3'-UTR of the Bcl-X(L) mRNA and could stabilize the mRNA in vitro. Furthermore, overexpression of nucleolin stabilizes the Bcl-X(L) mRNA in HeLa cells, whereas reducing nucleolin by small interfering RNA shortens the Bcl-X(L) mRNA half-life. Interestingly, nucleolin physically interacted with polyadenylate [poly(A)]-binding protein through it RGG motifs. Its stabilizing effect on the Bcl-X(L) mRNA was dependent upon the presence of poly(A) tail. Based on these data, we propose a model in which nucleolin protects the Bcl-X(L) mRNA from nuclease degradation by enhancing the stability of the ribonucleoprotein loop structure.

MeSH Terms
3' Untranslated Regions HeLa Cells Humans Keratinocytes/metabolism,radiation effects Phosphoproteins/genetics,metabolism Poly(A)-Binding Proteins/metabolism Protein Binding RNA, Messenger/metabolism,radiation effects RNA-Binding Proteins/genetics,metabolism Transfection Ultraviolet Rays bcl-X Protein/genetics
Chemicals
3' Untranslated Regions BCL2L1 protein, human Phosphoproteins Poly(A)-Binding Proteins RNA, Messenger RNA-Binding Proteins bcl-X Protein nucleolin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Zhang Jack
Arizona Cancer Center, University of Arizona, Tuczon, Arizona 85724, USA.
Tsaprailis George
Bowden G Tim
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Article Info
Journal
Cancer research
Abbr.
Cancer Res
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-07-1927
Published
2008-02-15
Pages
1046-54
Language
English
Region
United States
NLM ID
2984705R
PMCID
PMC2373251
Subset
IM
Grants
NCI NIH HHS · CA40584 · United States
NCI NIH HHS · P30 CA023074 · United States
NCI NIH HHS · R01 CA040584-22 · United States
NCI NIH HHS · CA23074 · United States
NCI NIH HHS · R01 CA040584 · United States
NCI NIH HHS · P01 CA027502-26 · United States
NCI NIH HHS · P01 CA027502 · United States
NIEHS NIH HHS · ES06694 · United States
NIEHS NIH HHS · P30 ES006694 · United States
NCI NIH HHS · CA27502 · United States
NCI NIH HHS · P30 CA023074-28 · United States
External Links
PubMed source DOI: 10.1158/0008-5472.CAN-07-1927 PMC Full Text View journal details
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