Death-effector domain-containing protein DEDD is an inhibitor of mitotic Cdk1/cyclin B1.
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.
Arai
Satoko
S
Division of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Tokyo 113-0033, Japan.
Miyake
Katsuhisa
K
Voit
Renate
R
Nemoto
Shino
S
Wakeland
Edward K
EK
Grummt
Ingrid
I
Miyazaki
Toru
T
D000818:Animals; D049628:Body Size; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D019926:Cyclin B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056744:Cyclin B1; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts; D007399:Interphase / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis / Q000502:physiology*; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D009929:Organ Size; D011485:Protein Binding; D012335:RNA, Ribosomal / Q000096:biosynthesis
C534700:Ccnb1 protein, mouse; D019926:Cyclin B; D056744:Cyclin B1; D053418:Death Domain Receptor Signaling Adaptor Proteins; C486432:Dedd protein, mouse; D046912:Multiprotein Complexes; D012335:RNA, Ribosomal; D016203:CDC2 Protein Kinase