The AAA-ATPase Cdc48/p97 regulates spindle disassembly at the end of mitosis

Cell. 2003 Oct 31;115(3):355-67. doi: 10.1016/s0092-8674(03)00815-8.

Abstract

Spindle disassembly at the end of mitosis is a complex and poorly understood process. Here, we report that the AAA-ATPase Cdc48/p97 and its adapters Ufd1-Npl4, which have a well-established role in membrane functions, also regulate spindle disassembly by modulating microtubule dynamics and bundling at the end of mitosis. In the absence of p97-Ufd1-Npl4 function, microtubules in Xenopus egg extracts remain as monopolar spindles attached to condensed chromosomes after Cdc2 kinase activity has returned to the interphase level. Consequently, interphase microtubule arrays and nuclei are not established. Genetic analyses of Cdc48, the yeast homolog of p97, reveal that Cdc48 is also required for disassembly of mitotic spindles after execution of the mitotic exit pathway. Furthermore, Cdc48/p97-Ufd1-Npl4 directly binds to spindle assembly factors and regulates their interaction with microtubules at the end of mitosis. Therefore, Cdc48/p97-Ufd1-Npl4 is an essential chaperone that regulates transformation of the microtubule structure as cells reenter interphase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Cell Cycle Proteins / metabolism
  • Cyclin B / metabolism
  • Interphase
  • Macromolecular Substances
  • Microtubule-Associated Proteins / metabolism
  • Mitosis*
  • Nuclear Proteins / metabolism*
  • Oocytes / cytology
  • Oocytes / enzymology
  • Protein Binding
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins / metabolism
  • Spindle Apparatus / enzymology*
  • Spindle Apparatus / metabolism*
  • Valosin Containing Protein
  • Xenopus Proteins / metabolism*
  • Xenopus laevis

Substances

  • Ase1 protein, S cerevisiae
  • CEF1 protein, S cerevisiae
  • CLB2 protein, S cerevisiae
  • Cell Cycle Proteins
  • Cyclin B
  • Macromolecular Substances
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Xenopus Proteins
  • Adenosine Triphosphatases
  • p97 ATPase
  • CDC48 protein, S cerevisiae
  • Valosin Containing Protein