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Sci. STKE, 20 July 2004
Vol. 2004, Issue 242, p. pe31
[DOI: 10.1126/stke.2422004pe31]

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Interwoven Ubiquitination Oscillators and Control of Cell Cycle Transitions

Xiaolu L. Ang and J. Wade Harper*

Program in Biological and Biomedical Sciences, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.

Abstract: Ubiquitin-mediated proteolysis has emerged as a paramount mechanism for regulating the cell division cycle. Changes in the activities of certain E3 ligases can promote the interconversion of cell cycle states or transitions. Recent studies have revealed how distinct E3 ligases control the activity of other E3 ligases and how the interplay between these degradation machines sets up the timing of cell cycle transitions. For example, during G1, the anaphase-promoting complex in conjunction with Cdh1 (APCCdh1) catalyzes destruction of the S-phase activator Skp2, helping to define the G1 state. In response to poorly defined signals, APCCdh1 activity is reduced, allowing accumulation of Skp2 and therefore entry into S phase. In many cases, E3 ligases also function to ubiquitinate proteins that negatively regulate cell cycle transitions. Recent work indicates that cyclin-dependent kinase 2 and Polo kinase collaborate to phosphorylate Wee1, thereby promoting its ubiquitination by SCFβ-TRCP. Thus, activation of the mitotic transition produces feedback signals that help to turn off the negative upstream pathway to further reenforce the transition.

*Corresponding author. E-mail: wade_harper{at}hms.harvard.edu

Citation: X. L. Ang, J. W. Harper, Interwoven Ubiquitination Oscillators and Control of Cell Cycle Transitions. Sci. STKE 2004, pe31 (2004).

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