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

  • J Biol Chem. 2004 Mar 5;279(10):8642-7. doi: 10.1074/jbc.M311466200.
Veerle Vulsteke  1 ,  Monique Beullens ,  An Boudrez ,  Stefaan Keppens ,  Aleyde Van Eynde ,  Mark H Rider ,  Willy Stalmans ,  Mathieu Bollen
Affiliations
  • 1. Afdeling Biochemie, Faculteit Geneeskunde, Catholic University of Leuven, B-3000 Leuven, Belgium.
PMID: 14699119 DOI: 10.1074/jbc.M311466200
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.