The N-terminal fragment from caspase-cleaved serine/arginine protein-specific kinase2 (SRPK2) translocates into the nucleus and promotes apoptosis.
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.
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Yi
Y
Hong
Sung-Wuk
SW
Jang
Keqiang
K
Ye
D048948:14-3-3 Proteins / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D017209:Apoptosis / Q000187:drug effects; D001224:Aspartic Acid; D001665:Binding Sites; D020169:Caspases / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D048948:14-3-3 Proteins; D010446:Peptide Fragments; D001224:Aspartic Acid; D005047:Etoposide; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases