Cdc20 hypomorphic mice fail to counteract de novo synthesis of cyclin B1 in mitosis.
Cdc20 is an activator of the anaphase-promoting complex/cyclosome that initiates anaphase onset by ordering the destruction of cyclin B1 and securin in metaphase. To study the physiological significance of Cdc20 in higher eukaryotes, we generated hypomorphic mice that express small amounts of this essential cell cycle regulator. In this study, we show that these mice are healthy and not prone to cancer despite substantial aneuploidy. Cdc20 hypomorphism causes chromatin bridging and chromosome misalignment, revealing a requirement for Cdc20 in efficient sister chromosome separation and chromosome-microtubule attachment. We find that cyclin B1 is newly synthesized during mitosis via cytoplasmic polyadenylation element-binding protein-dependent translation, causing its rapid accumulation between prometaphase and metaphase of Cdc20 hypomorphic cells. Anaphase onset is significantly delayed in Cdc20 hypomorphic cells but not when translation is inhibited during mitosis. These data reveal that Cdc20 is particularly rate limiting for cyclin B1 destruction because of regulated de novo synthesis of this cyclin after prometaphase onset.
Malureanu
Liviu
L
Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Jeganathan
Karthik B
KB
Jin
Fang
F
Baker
Darren J
DJ
van Ree
Janine H
JH
Gullon
Oliver
O
Chen
Zheyan
Z
Henley
John R
JR
van Deursen
Jan M
JM
D020413:3' Untranslated Regions; D000782:Aneuploidy; D000818:Animals; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D020090:Chromosome Segregation; D033481:Chromosomes, Mammalian / Q000378:metabolism; D056744:Cyclin B1 / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D018386:Kinetochores / Q000378:metabolism; D051379:Mice; D008938:Mitosis; D009369:Neoplasms / Q000235:genetics; D055495:Neurogenesis / Q000235:genetics; D014176:Protein Biosynthesis
D020413:3' Untranslated Regions; C534700:Ccnb1 protein, mouse; D064199:Cdc20 Proteins; C577491:Cdc20 protein, mouse; D018797:Cell Cycle Proteins; D056744:Cyclin B1