Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10895577 | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer | 2014 | 17 Pages |
Abstract
The Anaphase Promoting Complex/Cyclosome (APC/C) is a multi-subunit E3 ubiquitin ligase that primarily governs cell cycle progression. APC/C is composed of at least 14 core subunits and recruits its substrates for ubiquitination via one of the two adaptor proteins, Cdc20 or Cdh1, in M or M/early G1 phase, respectively. Furthermore, recent studies have shed light on crucial functions for APC/C in maintaining genomic integrity, neuronal differentiation, cellular metabolism and tumorigenesis. To gain better insight into the in vivo physiological functions of APC/C in regulating various cellular processes, particularly development and tumorigenesis, a number of mouse models of APC/C core subunits, coactivators or inhibitors have been established and characterized. However, due to their essential role in cell cycle regulation, most of the germline knockout mice targeting the APC/C pathway are embryonic lethal, indicating the need for generating conditional knockout mouse models to assess the role in tumorigenesis for each APC/C signaling component in specific tissues. In this review, we will first provide a brief introduction of the ubiquitin-proteasome system (UPS) and the biochemical activities and cellular functions of the APC/C E3 ligase. We will then focus primarily on characterizing genetic mouse models used to understand the physiological roles of each APC/C signaling component in embryogenesis, cell proliferation, development and carcinogenesis. Finally, we discuss future research directions to further elucidate the physiological contributions of APC/C components during tumorigenesis and validate their potentials as a novel class of anti-cancer targets.
Keywords
MCChomologous to the E6-AP carboxyl terminusMitotic checkpoint complexBub3Skp1BubR1Fbw7β-TrCP4-OHTRASSF1AHECTanaphase promoting complex/cyclosomeCDC20CDH1L-LTP4-hydroxytamoxifentPASACAOMazoxymethaneSCFDMBA12-O-tetradecanoylphorbol-13-acetateAPC/Cubiquitin ligaseEmi1spindle assembly checkpointTransgenic expressionTumorigenesisRingUbiquitin-proteasome systemMad2Mouse modelknockoutβ-transducin repeat-containing proteinCell cycle progressionreally interesting new geneUPSUbiquitin
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Authors
Jinfang Zhang, Lixin Wan, Xiangpeng Dai, Yi Sun, Wenyi Wei,