Mechanism of cell-cycle control: ligating the ligase

Trends in Biochemical Sciences
Douglas I Lin, J Alan Diehl

Abstract

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.

References

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Citations

Sep 8, 2007·The Journal of Clinical Investigation·Lingwen ZhongAnil Bhushan
Aug 5, 2009·Biological & Pharmaceutical Bulletin·Noemí BoquéJosé Alfredo Martinez
Aug 12, 2006·The EMBO Journal·Günter SchneiderRoland M Schmid
Jun 27, 2009·Comparative and Functional Genomics·Yafang ShenYaozhou Zhang
May 3, 2016·Journal of Animal Science·E A StaigerS A Brooks

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