Two distinct controls of mitotic cdk1/cyclin B1 activity requisite for cell growth prior to cell division

Cell Cycle. 2007 Jun 15;6(12):1419-25. Epub 2007 May 7.


Cell growth prior to cell division is restricted by the activity of cyclin-dependent kinase 1 (Cdk1)/cyclin B1 complexes. Recently, we identified that the death-effector domain (DED) containing protein, DEDD, acts as a novel inhibitor of mitotic Cdk1/cyclin B1, influencing cell size. Like cyclin B1, DEDD protein levels specifically peak during the G(2)/M phase. In the nucleus, DEDD associates with Cdk1/cyclin B1 complexes, via direct binding to cyclin B1, and reduces their function. In agreement, kinase activity of nuclear Cdk1/cyclin B1 in DEDD-null (DEDD(-/-)) embryonic fibroblasts is increased compared to that in DEDD(+/+) cells. This accelerates mitotic progression in DEDD(-/-) cells, with a shortened G(2)/M phase, reduced rRNA, and diminished cell volume. Likewise, DEDD(-/-) mice show decreased body and organ weights relative to DEDD(+/+) mice. Interestingly, the DED domain is not involved in the association of DEDD with Cdk1/cyclin B1, but is indispensable for the cell sizing function of DEDD. Together, in addition to the well-established machinery for activation of Cdk1 through dephosphorylation of its inhibitory-residues, we propose a novel mechanism for impeditive regulation of mitotic Cdk1/cyclin B1 mediated by DEDD within the nucleus, which allows sufficient cell growth prior to cell division.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Body Size / physiology*
  • CDC2 Protein Kinase / metabolism*
  • Cell Cycle / physiology*
  • Cell Enlargement*
  • Cyclin B / metabolism*
  • Cyclin B1
  • Death Domain Receptor Signaling Adaptor Proteins / genetics
  • Death Domain Receptor Signaling Adaptor Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Mitosis / physiology
  • Models, Biological*


  • Ccnb1 protein, mouse
  • Cyclin B
  • Cyclin B1
  • Death Domain Receptor Signaling Adaptor Proteins
  • Dedd protein, mouse
  • CDC2 Protein Kinase