Death-effector domain-containing protein DEDD is an inhibitor of mitotic Cdk1/cyclin B1

Satoko Arai, Katsuhisa Miyake, Renate Voit, Shino Nemoto, Edward K. Wakeland, Ingrid Grummt, Toru Miyazaki

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Accumulating evidence has shown that many molecules, including some cyclin-dependent kinases (Cdks) and cyclins, as well as the death-effector domain (DED)-containing FADD, function for both apoptosis and cell cycle. Here we identified that DEDD, which also possesses the DED domain, acts as a novel inhibitor of the mitotic Cdk1/cyclin B1 complex. DEDD associates with mitotic 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 with that in DEDD+/+ cells, which results in accelerated mitotic progression, thus exhibiting a shortened G2/M stage, interestingly, DEDD-/- cells also demonstrated decreased G1 duration, which perhaps enhanced the overall reduction in rRNA amounts and cell volume, primarily caused by the rapid termination of rRNA synthesis before cell division. Likewise, DEDD-/- mice show decreased body and organ weights relative to DEDD+/+ mice. Thus, DEDD is an impeder of cell mitosis, and its absence critically influences cell and body size via modulation of rRNA synthesis.

Original languageEnglish (US)
Pages (from-to)2289-2294
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number7
DOIs
StatePublished - Feb 13 2007

Fingerprint

Death Domain Receptor Signaling Adaptor Proteins
Cyclin B1
Cell Size
Null Lymphocytes
Cyclins
Organ Size
Cyclin-Dependent Kinases
Body Size
Mitosis
Cell Division
Cell Cycle
Phosphotransferases
Fibroblasts
Body Weight
Apoptosis

Keywords

  • Apoptosis
  • Cell cycle
  • Cell size
  • Cyclin-dependent kinase
  • Mitosis

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Death-effector domain-containing protein DEDD is an inhibitor of mitotic Cdk1/cyclin B1. / Arai, Satoko; Miyake, Katsuhisa; Voit, Renate; Nemoto, Shino; Wakeland, Edward K.; Grummt, Ingrid; Miyazaki, Toru.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 7, 13.02.2007, p. 2289-2294.

Research output: Contribution to journalArticle

Arai, Satoko ; Miyake, Katsuhisa ; Voit, Renate ; Nemoto, Shino ; Wakeland, Edward K. ; Grummt, Ingrid ; Miyazaki, Toru. / Death-effector domain-containing protein DEDD is an inhibitor of mitotic Cdk1/cyclin B1. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 7. pp. 2289-2294.
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