Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1

Vulsteke, V;Beullens, M;Boudrez, A;Keppens, S.;Bollen, M.;et.al.

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Authors
  • Vulsteke, V
    Author
  • Beullens, M
    Author
  • Boudrez, A
    Author
  • Keppens, S.
    Author
  • Rider, Mark H.UCLouvain
    Author
  • Bollen, M.
    Author
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Abstract
NIPP1 is a ubiquitous nuclear protein that is required for spliceosome assembly. We report here that the phosphothreonine-binding Forkhead-associated domain of NIPP1 interacts with the cell cycle-regulated protein Ser/Thr kinase MELK ( maternal embryonic leucine zipper kinase). The NIPP1-MELK interaction was critically dependent on the phosphorylaton of Thr-478 of MELK and was increased in lysates from mitotically arrested cells. Recombinant MELK was a potent inhibitor of an early step of spliceosome assembly in nuclear extracts. This splicing defect was also seen with a kinase-dead mutant but was absent after mutation (T478A) of the NIPP1 binding site of MELK, indicating a mediatory role for NIPP1. Our data suggest that MELK has a role in the cell cycle-regulated control of pre-mRNA splicing.
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