Imperial College London
Portrait Picture

Dr Olivier E. Pardo

Faculty of Medicine, Department of Surgery & Cancer

Reader in Cancer Cell Signalling
 
 
 
//

Contact

 

+44 (0)20 7594 2814o.pardo Website CV

 
 
//

Location

 

145ICTEM buildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Roy:2014:nar/gku953,
author = {Roy, R and Durie, D and Li, H and Liu, B-Q and Skehel, JM and Mauri, F and Cuorvo, LV and Barbareschi, M and Guo, L and Holcik, M and Seckl, MJ and Pardo, OE},
doi = {nar/gku953},
journal = {Nucleic Acids Research},
pages = {12483--12497},
title = {hnRNPA1 couples nuclear export and translation of specific mRNAs downstream of FGF-2/S6K2 signalling},
url = {http://dx.doi.org/10.1093/nar/gku953},
volume = {42},
year = {2014}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The increased cap-independent translation of anti-apoptotic proteins is involved in the development of drug resistance in lung cancer but signalling events regulating this are poorly understood. Fibroblast growth factor 2 (FGF-2) signalling-induced S6 kinase 2 (S6K2) activation is necessary, but the downstream mediator(s) coupling this kinase to the translational response is unknown. Here, we show that S6K2 binds and phosphorylates hnRNPA1 on novel Ser4/6 sites, increasing its association with BCL-XL and XIAP mRNAs to promote their nuclear export. In the cytoplasm, phosphoS4/6-hnRNPA1 dissociates from these mRNAs de-repressing their IRES-mediated translation. This correlates with the phosphorylation-dependent association of hnRNPA1 with 14-3-3 leading to hnRNPA1 sumoylation on K183 and its re-import into the nucleus. A non-phosphorylatible, S4/6A mutant prevented these processes, hindering the pro-survival activity of FGF-2/S6K2 signalling. Interestingly, immunohistochemical staining of lung and breast cancer tissue samples demonstrated that increased S6K2 expression correlates with decreased cytoplasmic hnRNPA1 and increased BCL-XL expression. In short, phosphorylation on novel N-term sites of hnRNPA1 promotes translation of anti-apoptotic proteins and is indispensable for the pro-survival effects of FGF-2.
AU  - Roy,R
AU  - Durie,D
AU  - Li,H
AU  - Liu,B-Q
AU  - Skehel,JM
AU  - Mauri,F
AU  - Cuorvo,LV
AU  - Barbareschi,M
AU  - Guo,L
AU  - Holcik,M
AU  - Seckl,MJ
AU  - Pardo,OE
DO  - nar/gku953
EP  - 12497
PY  - 2014///
SN  - 0305-1048
SP  - 12483
TI  - hnRNPA1 couples nuclear export and translation of specific mRNAs downstream of FGF-2/S6K2 signalling
T2  - Nucleic Acids Research
UR  - http://dx.doi.org/10.1093/nar/gku953
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000347693200019&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://academic.oup.com/nar/article/42/20/12483/2903192
UR  - http://hdl.handle.net/10044/1/21577
VL  - 42
ER  -
Download