TI - The splicing factor SF2/ASF regulates translation initiation by enhancing phosphorylation of 4E-BP1 . AB - The SR protein SF2/ASF has been initially characterized as a splicing factor but has also been shown to mediate postsplicing activities such as mRNA export and translation . Here we demonstrate that SF2/ASF promotes translation initiation of bound mRNAs and that this activity requires the presence of the cytoplasmic cap-binding protein eIF4E . SF2/ASF promotes translation initiation by suppressing the activity of 4E-BP , a competitive inhibitor of cap -dependent translation . This activity is mediated by interactions of SF2/ASF with both mTOR and the phosphatase PP2A , two key regulators of 4E-BP phosphorylation . These findings suggest the model whereby SF2/ASF functions as an adaptor protein to recruit the signaling molecules responsible for regulation of cap -dependent translation of specific mRNAs . Taken together , these data suggest a novel mechanism for the activation of translation initiation of a subset of mRNAs bound by the shuttling protein SF2/ASF .