APC/C plays a key role in mitotic exit and has essential targets in the G1 phase; however, these mechanisms are poorly understood. In this report, we provide evidence that DDB1 (Damaged DNA binding protein 1) is capable of binding the WD40 domains of Cdh1, but not of Cdc20, through its BPA and BPC domains. Moreover, cells lacking DDB1 exhibit markedly elevated levels of the protein substrates o...

Long noncoding RNA (lncRNA) has been implicated in cancer, but little is known about the role of lncRNAs as regulators of tumor metastasis. In the present study, we demonstrate that lncRNA TRERNA1 acts like an enhancer of SNAI1 to promote cell invasion and migration and to contribute to metastasis of gastric cancer (GC). TRERNA1 is significantly unregulated in GCs and GC cell lines. Increased T...

We have found that key mitotic regulators show distinct patterns of degradation during exit from mitosis in human cells. Using a live-cell assay for proteolysis, we show that two of these regulators, polo-like kinase 1 (Plk1) and Aurora A, are degraded at different times after the anaphase-promoting complex/cyclosome (APC/C) switches from binding Cdc20 to Cdh1. Therefore, events in addition to ...

Cdc20 and cdh1 are coactivators of the anaphase-promoting complex (APC). APC(cdc20) is necessary for the metaphase-anaphase transition and, at the end of mitosis, vertebrate cdc20 itself becomes a target for degradation through KEN-box-dependent APC(cdh1) activity. By studying the degradation of fluorescent protein chimaeras in mammalian oocytes and early embryos, we found that cdc20 was degrad...

Regulated degradation plays a key role in setting the level of many factors that govern cell cycle progression. In Drosophila, the largest subunit of the origin recognition complex protein 1 (ORC1) is degraded at the end of M phase and throughout much of G1 by anaphase-promoting complexes (APC) activated by Fzr/Cdh1. We show here that none of the previously identified APC motifs targets ORC1 fo...

In response to DNA damage in G2, mammalian cells must avoid entry into mitosis and instead initiate DNA repair. Here, we show that, in response to genotoxic stress in G2, the phosphatase Cdc14B translocates from the nucleolus to the nucleoplasm and induces the activation of the ubiquitin ligase APC/C(Cdh1), with the consequent degradation of Plk1, a prominent mitotic kinase. This process induce...

Proapoptotic Bcl-2 family members, such as Bax, promote release of cytochrome c from mitochondria, leading to caspase activation and cell death. It was previously reported that modulator of apoptosis protein 1 (MOAP-1), an enhancer of Bax activation induced by DNA damage, is stabilized by Trim39, a protein of unknown function. In this paper, we show that MOAP-1 is a novel substrate of the anaph...

PURPOSE This study aims to identify downstream target genes regulated by lysine-specific demethylase 1 (LSD1) in colon cancer cells and investigate the molecular mechanisms of LSD1 influencing invasion and metastasis of colon cancer. METHOD We obtained the expression changes of downstream target genes regulated by small-interfering RNA-LSD1 and LSD1-overexpression via gene expression profilin...

Cadherins are cell-to-cell adhesion molecules that play an important role in the establishment of adherent-type junctions by mediating calcium-dependent cellular interactions. The CDH1 gene encodes the transmembrane glycoprotein E-cadherin which is important in maintaining homophilic cell-cell adhesion in epithelial tissues. E-cadherin interacts with catenin proteins to maintain tissue architec...

Bleach at the roots of mitotic progression Lim et al. show how hydrogen peroxide at the centrosome spurs cells to advance through mitosis. Cdk1 and regulatory proteins such as cyclin B1, Plk1, and Aurora A cooperate to initiate mitosis. To exit mitosis, cells destroy the regulatory proteins, an effect triggered by the APC/C when it is bound to its coactivator Cdh1. Cdk1 adds phosphates to Cdh1 ...