Mechanism of cell-cycle control: ligating the ligase.
The F-box protein SKP2 promotes the G1-S transition by targeting key regulators for proteasomal degradation via its capacity to function as the specificity factor for the SKP1 Cullin F-box SCF(SKP2) ubiquitin ligase. SKP2 is a labile protein, the levels of which oscillate in a cell cycle-dependent manner. SKP2 accumulation is often deregulated in cancer, which indicates that temporal control of SKP2 is essential for normal cell proliferation. Two new studies now suggest that SKP2 accumulation is determined by a second ubiquitin ligase, the anaphase-promoting complex or cyclosome, APC/C(CDH1). These studies highlight a novel mechanism wherein mitotic machinery communicates with proteins that regulate G1 phase progression.
Lin
Douglas I
DI
The Leonard and Madlyn Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson Family Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Diehl
J Alan
JA
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D016193:G1 Phase; D006801:Humans; D008025:Ligases / Q000378:metabolism*; D016196:S Phase; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism
D044786:S-Phase Kinase-Associated Proteins; D008025:Ligases