Dobrynin, Grzegorz; Popp, Oliver; Romer, Tina; Bremer, Sebastian; Schmitz, Michael H. A.; Gerlich, Daniel W.; Meyer, Hemmo:

Cdc48/p97-Ufd1-Npl4 antagonizes Aurora B during chromosome segregation in HeLa cells.

In: Journal of Cell Science, Jg. 124 (2011) ; Nr. 9, S. 1571-1580
ISSN: 0021-9533
Zeitschriftenaufsatz / Fach: Biologie
Fakultät für Biologie » Chemische Biologie
Abstract:
During exit from mitosis in Xenopus laevis egg extracts, the AAA+ ATPase
   Cdc48/p97 (also known as VCP in vertebrates) and its adapter Ufd1-Npl4
   remove the kinase Aurora B from chromatin to allow nucleus formation.
   Here, we show that in HeLa cells Ufd1-Npl4 already antagonizes Aurora B
   on chromosomes during earlier mitotic stages and that this is crucial
   for proper chromosome segregation. Depletion of Ufd1-Npl4 by small
   interfering RNA (siRNA) caused chromosome alignment and anaphase defects
   resulting in missegregated chromosomes and multi-lobed nuclei. Ufd1-Npl4
   depletion also led to increased levels of Aurora B on prometaphase and
   metaphase chromosomes. This increase was associated with higher Aurora B
   activity, as evidenced by the partial resistance of CENP-A
   phosphorylation to the Aurora B inhibitor hesperadin. Furthermore, low
   concentrations of hesperadin partially rescued chromosome alignment in
   Ufd1-depleted cells, whereas, conversely, Ufd1-depletion partially
   restored congression in the presence of hesperadin. These data establish
   Cdc48/p97-Ufd1-Npl4 as a crucial negative regulator of Aurora B early in
   mitosis of human somatic cells and suggest that the activity of Aurora B
   on chromosomes needs to be restrained to ensure faithful chromosome
   segregation.