Archives for category: Meeting

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Tom Kucharski from the Teodoro Lab presented a talk at the recent cell cycle meeting at Cold Spring Harbor Laboratory entitled: “53BP1 is a novel anaphase promoting complex/cyclosome mitotic substrate and regulator”. 

Abstract

Cells respond to DNA damage through highly conserved mechanisms that result in the rapid recruitment of repair factors to sites known as ionizing radiation induced foci (IRIFs). Among such factors is the repair protein53BP1, which is a tumour suppressor known for its role in promoting DNA repair through the Non-homologous End Joining pathway (NHEJ).  The Anaphase Promoting Complex/Cyclosome is an E3 Ubiquitin Ligase whose activity is essential for proper mitotic progression. APC/C activity is therefore tightly regulated by a combination of post-translational modifications, co-activator proteins, and inhibitory proteins such as EMI and RASSF1A. Here we show that 53BP1 is itself a target of the APC/C during mitosis and that this regulation is important in the control of mitotic progression. 53BP1 contains three highly conserved KEN boxes that are required for its APC/C and proteasome dependent degradation during prometaphase, which occurs both during unperturbed mitosis and also under an active Spindle Assembly Checkpoint. Accordingly, 53BP1 is heavily ubiquitinated during mitosis through K11 linked Ubiquitin chains, a recently discovered hallmark of APC/C substrates. We also show that 53BP1 is constitutively bound to the APC/C co-activator cdc20 and crucially, inhibits its activity. However, binding of 53BP1 to cdc20 in interphase cells does not require the KEN boxes, but instead requires the tandem BRCT repeats of 53BP1. Silencing of 53BP1 expression results in a decrease in the levels of most APC/C substrates, which does not disturb cell proliferation under normal conditions, but is lethal when the cells are faced with the spindle poisons Nocodazole or Taxol. We therefore propose that 53BP1 may be a novel APC/C inhibitor. Consistent with this hypothesis, the half-lives of APC/C substrates are shortened in the absence of 53BP1, and the substrates are more extensively ubiquitinated. The degradation of 53BP1 in early mitosis, therefore appears to allow proper temporal activation of the APC/C and prevent premature mitotic entry, and thus likely contributes to the tumour suppressor status of 53BP1.

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Joe Teodoro recently presented a talk at BIotransfer 2014 in Toronto. The presentation was following up the use of a PTEN regulated factor identified in the lab as a potential prostate cancer biomarker. Biotransfer brings together industry and academia to promote the commercialization of scientific discoveries. A video of the talk is available at the following link

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Two abstracts were presented by the lab this year at the DNATV meeting in Birmingham, UK.  Thomas Kucharski presented a poster “Characterization of the Human Gyrovirus Type Interaction with the Anaphase-Promoting Complex” and Joe Teodoro presented an oral presentation entitled “Interaction of Adenovirus type 5 E4orf4 with the nucleoporin subunit Nup205 us required for proper viral gene expression”.

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DNATVmtl

The DNA tumour virus meeting was held in Canada for the first time in its long history. This meeting has occurred yearly since 1969. The conference was held at the Centre Mont-Royal just across from the Roddick Gates at McGill University. Nearly 200 researchers attended the 5 day meeting.  Next year’s meeting has been tentatively scheduled to take place in Oxford, UK. Two abstracts were presented by members of the Teodoro lab.  Yiquing Lu presented a poster entitled: “Human Adenovirus Type 5 E4orf4 Interacts with the Nucleopore Component Nup205 to Regulate Viral Gene Expression and Enhance Virus Replication.”  Mohamed Mustafa presented the poster “The Chicken Anemia Virus Protein Apoptin Binds and Inhibits the Anaphase-Promoting Complex Through an Essential IR motif”.

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Sarah Assadian presented a poster in Leuven, Belgium at the Cell Angiogenesis Symposia.  Her abstract was entitled: “The p53 Tumor Supressor Inhibits Angiogenesis by Inducing Expression and Processing of Collagen IV into the Anti-angiogenic Protein Arresten.”

Yiquing Lu presented his research at a meeting at the University of Alberta entitled “Meeting the Challenge of Emerging, Acute and Persistent Viral Diseases”. 

 

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