Polypyrimidine tract binding protein regulates IRES-mediated gene expression during apoptosis

Bushell, M. , Stoneley, M., Kong, Y. W., Hamilton, T. L., Spriggs, K. A., Dobbyn, H. C., Qin, X., Sarnow, P. and Willis, A. E. (2006) Polypyrimidine tract binding protein regulates IRES-mediated gene expression during apoptosis. Molecular Cell, 23(3), pp. 401-412. (doi: 10.1016/j.molcel.2006.06.012) (PMID:16885029)

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Abstract

During apoptosis there is a substantial reduction in the rate of protein synthesis, and yet some mRNAs avoid this translational inhibition. To determine the impact that receptor-mediated cell death has on the translational efficiency of a large number of mRNAs, translational profiling was performed on MCF7 cells treated with the apoptosis-inducing ligand TRAIL. Our data indicate that approximately 3% of mRNAs remain associated with the polysomes in apoptotic cells, and genes that are involved in transcription, chromatin modification/remodeling, and the Notch signaling pathway are particularly prevalent among the mRNAs that evade translational inhibition. Internal ribosome entry segments (IRESs) were identified in several of the mRNAs that remained associated with the polysomes during apoptosis, and, importantly, these IRESs functioned efficiently in apoptotic cells. Finally, the data showed that polypyrimidine tract binding protein (PTB, a known IRES trans-acting factor or ITAF) is pivotal in regulating the apoptotic process by controlling IRES function.

Item Type:Articles
Additional Information:This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (M.B., M.S., Y.W.K., T.L.H., H.C.D., and A.E.W.), the National Institutes of Health (X.Q. and P.S.), and the Wellcome Trust (M.B., International Travelling Fellowship 063233/B/00/Z; and K.A.S.). M.B. is a David Phillips Fellow (BBSRC).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bushell, Professor Martin
Authors: Bushell, M., Stoneley, M., Kong, Y. W., Hamilton, T. L., Spriggs, K. A., Dobbyn, H. C., Qin, X., Sarnow, P., and Willis, A. E.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Molecular Cell
Publisher:Elsevier
ISSN:1097-2765
ISSN (Online):1097-4164
Published Online:03 August 2006

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