TY - JOUR
T1 - Interwoven ubiquitination oscillators and control of cell cycle transitions.
AU - Ang, Xiaolu L.
AU - Harper, J. Wade
PY - 2004/7/20
Y1 - 2004/7/20
N2 - 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 (APC(Cdh1)) catalyzes destruction of the S-phase activator Skp2, helping to define the G1 state. In response to poorly defined signals, APC(Cdh1) 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 SCF(beta-TRCP). Thus, activation of the mitotic transition produces feedback signals that help to turn off the negative upstream pathway to further reenforce the transition.
AB - 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 (APC(Cdh1)) catalyzes destruction of the S-phase activator Skp2, helping to define the G1 state. In response to poorly defined signals, APC(Cdh1) 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 SCF(beta-TRCP). Thus, activation of the mitotic transition produces feedback signals that help to turn off the negative upstream pathway to further reenforce the transition.
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U2 - 10.1126/stke.2422004pe31
DO - 10.1126/stke.2422004pe31
M3 - Review article
C2 - 15266102
AN - SCOPUS:19344375385
SN - 1937-9145
VL - 2004
SP - pe31
JO - Science's STKE : signal transduction knowledge environment
JF - Science's STKE : signal transduction knowledge environment
IS - 242
ER -