page 245, Culjkovic et al. show that a promiscuous translation factor carries out a more selective function in the nucleus.
The promiscuous function of the eIF4E translation initiation factor is to bring all mRNAs to the ribosome. Although transcript sequences vary greatly, eIF4E recognizes them all by their ubiquitous 5′ cap structure. A less well-understood function of eIF4E, however, lies in its ability to export specific transcripts from the nucleus, thus increasing the amount available for translation. Only two transcripts have so far been shown to be exported by eIF4E—cyclin D1 and ornithine decarboxylase (ODC).
The new results map eIF4E's export selectivity to a 100-bp sequence in the cyclin D1 3′ UTR, which the authors call the 4E-SE. eIF4E's cap-binding ability was also required for export. Another nuclear factor may increase the transcript's affinity for eIF4E by binding to both the UTR and eIF4E. The authors are currently looking for candidate proteins that may serve this function.
Recently, the group has found that ODC and several other cyclins also contain the 4E-SE. The activation of eIF4E (via growth factor MAPK pathways, for example) could thus result in rapid, transcription-independent growth and proliferation by triggering the export of a whole set of cell cycle–promoting transcripts. But the system can be dangerous, as high levels of eIF4E are associated with malignant cancers. The authors show that this transformation can be blocked by deletion of the cyclin D1 4E-SE.