|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
Cell Biology International (1999) 23, 275286 (Printed in Great Britain)
MUTATIONS IN THE ATP-BINDING DOMAIN AFFECT THE SUBCELLULAR DISTRIBUTION OF MITOTIC CENTROMERE-ASSOCIATED KINESIN (MCAK)
Linda Wordemanf1, Mike Wagenbach and Todd Maney
Department of Physiology and Biophysics, University of Washington School of Medicine, Box 357290, Seattle, WA, 98195, U.S.A.
Mitotic centromere-associated kinesin (MCAK) is important for anaphase chromosome segregation. MCAK is diffusely localized to both the cytoplasm and the nucleus during interphase. At prophase MCAK is recruited to mitotic centromeres. It is associated with centromeres throughout mitosis and then returns to exhibiting a diffuse nuclear and cytoplasmic localization during interphase. MCAK has several predicted nuclear localization sequences. The subcelluar distribution of expressed deletion constructs of GFP-MCAK suggest that the nucleocytoplasmic ratio of MCAK protein is dependent on a balance between several predicted nuclear localization sequences (NLS) and a putative nuclear exclusion sequence (NES) in the amino-terminal region of MCAK. Amino acid substitutions in the ATP-binding domain of the MCAK motor affect nuclear localization, which, in turn, influences the degree of centromere binding.
Key words: MCAK, kinesin, NLS, NES, centromere, rigor.
f1To whom correspondence should be addressed.
Received 11 November 1998; accepted 19 February 1999doi:10.1006/cbir.1999.0359