Posttranscriptional Regulation of Splicing Factor SRSF1 and Its Role in Cancer Cell Biology

Figure 1

Life cycle and posttranslational modifications of the SRSF1 protein. Following its de novo synthesis at ribosomes, the cytoplasmic SRSF1 protein is constitutively phosphorylated by the cytosolic protein kinase SRPK at serine residues in the proximal RS domain (pRS). This first phosphorylation step is required for nuclear import of SRSF1, followed by a second phosphorylation step at the distal RS domain (dRS), including several serine-proline (SP) motifs. This step is usually catalyzed by the nuclear protein kinase CLK1 but can also be performed by SRPK if induced to translocate into the nucleus. Nuclear translocation is further modulated through methylation of the three arginine residues R93, R97, and R109 located between the two RNA recognition motif (RRM) domains (not shown). SRSF1 with a completely phosphorylated RS domain accumulates in nuclear speckles from where it is recruited to the spliceosome. SRSF1 dephosphorylation induces its nuclear to cytoplasmic translocation and lack of phosphorylation by SRPK in the cytosol leads to its proteolytic degradation.