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From Rabbit Reticulocytes to Clam Oocytes: In Search of the System That Targets Mitotic Cyclins for Degradation

By the late 1980s, the basic biochemistry of ubiquitin-mediated protein degradation had already been elucidated by studies that used reticulocyte lysates. However, the scope and biological functions of this system remained largely obscure. Therefore, I became interested at that time in the mechanism...

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Detalles Bibliográficos
Autor principal: Hershko, Avram
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869371/
https://www.ncbi.nlm.nih.gov/pubmed/20335505
http://dx.doi.org/10.1091/mbc.E09-07-0583
Descripción
Sumario:By the late 1980s, the basic biochemistry of ubiquitin-mediated protein degradation had already been elucidated by studies that used reticulocyte lysates. However, the scope and biological functions of this system remained largely obscure. Therefore, I became interested at that time in the mechanisms by which mitotic cyclins are degraded in exit from mitosis. Using a cell-free system from clam oocytes that faithfully reproduced cell cycle stage–specific degradation of cyclins, we identified in 1995 a large ubiquitin ligase complex that targets mitotic cyclins for degradation. Subsequent studies in many laboratories showed that this ubiquitin ligase, now called the anaphase-promoting complex/cyclosome, has centrally important roles in many aspects of cell cycle control.