The function of APC/CCdh1 in cell cycle and beyond

Abstract

The anaphase promoting complex/cyclosome (APC/C) is a multi-subunit E3 ubiquitin ligase playing essential functions in mitosis. It is conserved from yeast to human and relies on two adaptor proteins, Cdc20 and Cdh1, to bring in substrates. Both APCCdc20 and APCCdh1 are implicated in the control of mitosis through mediating ubiquitination and degradation of important mitotic regulators such as cyclin B1, securin, and Plk1. In addition, APCCdh1 is thought to prevent premature S phase entry by limiting the accumulation of mitotic cyclins in G1 and to regulate processes unrelated to cell cycle. In this review, we will summarize our current understanding of APCCdh1 function in cell cycle and beyond.

Figure 1

Cdh1 regulate the timing of S-phase entry.

Figure 2

Cdh1 and cellular senescence. (A) Under normal conditions, the expression of p16 is tightly controlled by both positive and negative regulators. (B) Deletion of Cdh1 causes accumulation of Est2, leading to overexpression of p16 and senescence. (C) Oncogenic Ras may also induce senescence through Ets2.