Phosphorylation-Mediated Regulation of Alternative Splicing in Cancer

Figure 1

Phosphorylation-mediated regulation of SR proteins activity. Reversible phosphorylation of their RS domain profoundly affect SR protein (SRps) activity and subcellular localization. Newly synthesized SRps need SRPK-mediated phosphorylation in order to enter the nucleus and assemble in nuclear speckles. CLKs mediate SRps hyperphosphorylation and induce their release from nuclear speckles and their recruitment to transcription sites. Dephosphorylation of SRps is successively required for proper splicing catalysis. Moreover, dephosphorylated SRps facilitate export of spliced mRNA in the cytosol, where they enhance protein translation.