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SCF Fbxw5 targets kinesin‐13 proteins to facilitate ciliogenesis
Author(s) -
Schweiggert Jörg,
Habeck Gregor,
Hess Sandra,
Mikus Felix,
Beloshistov Roman,
Meese Klaus,
Hata Shoji,
Knobeloch KlausPeter,
Melchior Frauke
Publication year - 2021
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2021107735
Subject(s) - ciliogenesis , kinesin , biology , microbiology and biotechnology , microtubule , ubiquitin ligase , mitosis , ubiquitin , cell cycle , genetics , cilium , cell , gene
Microtubule depolymerases of the kinesin‐13 family play important roles in various cellular processes and are frequently overexpressed in different cancer types. Despite the importance of their correct abundance, remarkably little is known about how their levels are regulated in cells. Using comprehensive screening on protein microarrays, we identified 161 candidate substrates of the multi‐subunit ubiquitin E3 ligase SCF Fbxw5 , including the kinesin‐13 member Kif2c/MCAK. In vitro reconstitution assays demonstrate that MCAK and its closely related orthologs Kif2a and Kif2b become efficiently polyubiquitylated by neddylated SCF Fbxw5 and Cdc34, without requiring preceding modifications. In cells, SCF Fbxw5 targets MCAK for proteasomal degradation predominantly during G 2 . While this seems largely dispensable for mitotic progression, loss of Fbxw5 leads to increased MCAK levels at basal bodies and impairs ciliogenesis in the following G 1 /G 0 , which can be rescued by concomitant knockdown of MCAK, Kif2a or Kif2b. We thus propose a novel regulatory event of ciliogenesis that begins already within the G 2 phase of the preceding cell cycle.