Abstract
SRPK2 belongs to a family of serine/arginine (SR) protein-specific kinases (SRPKs), which phosphorylate SR domain-containing proteins in the nuclear speckles and mediate the pre-mRNA splicing. Previous studies have shown that SRPK2 plays a pivotal role in cell proliferation and apoptosis. However, how SRPK2 is regulated during the apoptosis is unclear. Here, we show that SRPK2 is cleaved by caspases at Asp-139 and -403 residues. Its N terminus cleaved product translocates into the nucleus and promotes VP16-induced apoptosis. Akt phosphorylation of SRPK2 prevents its apoptotic cleavage by caspases. 14-3-3β, the binding partner of Akt-phosphorylated SRPK2, further protects it from degradation. Hence, our results suggest that the N-terminal domain of SRPK2 cleaved by caspases translocates into the nucleus, where it promotes chromatin condensation and apoptotic cell death.
Highlights
Two families of kinases, SR protein-specific kinase (SRPK), and Clk/Sty, have been identified to phosphorylate SR domain-containing splicing factors
These data indicate that caspase 3 and 7 might be the major enzymes that contribute to its degradation. These results suggest that SRPK2 can be cleaved during apoptotic cell death in caspase-dependent manner, and SRPK2 may be the substrate of caspases
We show the direct evidence that SRPK2 is cleaved in vitro by recombinant caspase-3
Summary
SR protein-specific kinase (SRPK), and Clk/Sty, have been identified to phosphorylate SR domain-containing splicing factors. Caspase cleavage of SRPK2 releases its N-terminal fragment that translocates to the nucleus and further promotes apoptotic cell death. We observed that SRPK2 incubation with active Akt decreased its degradation (Fig. 3A), suggesting that Akt phosphorylation may protect SRPK2 from caspase cleavage.
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