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

Author:
Arai, Satoko, Miyake, Katsuhisa, Voit, Renate, Nemoto, Shino, Wakeland, Edward K., Grummt, Ingrid, Miyazaki, Toru
Source:
Proceedings of the National Academy of Sciences of the United States of America 2007 v.104 no.7 pp. 2289-2294
ISSN:
0027-8424
Subject:
apoptosis, body size, cyclin-dependent kinase, cyclins, fibroblasts, mice, mitosis, ribosomal RNA
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.
Agid:
2351595