The APC/C and CBP/p300 co-operate to regulate, transcription, transformation and progression through mitosis

The anaphase-promoting complex/cyclosome (APC/C) is a multicomponent E3 ubiquitin ligase that, by targeting protein substrates for 26S proteasome-mediated degradation through ubiquitination, coordinates the temporal progression of eukaryotic cells through mitosis and the subsequent G1 phase of the cell cycle. Other functions of the APC/C are, however, less well defined. Here we show that two APC/C components, APC5 and APC7, interact directly with the coactivators CBP and p300 through protein-protein interaction domains that are evolutionarily conserved in adenovirus E1A. This interaction stimulates intrinsic CBP/p300 acetyltransferase activity and potentiates CBP/p300-dependent transcription. We also show that APC5 and APC7 suppress E1A-mediated transformation in a CBP/p300-dependent manner, indicating that these components of the APC/C may be targeted during cellular transformation. Furthermore, we establish that CBP is required in APC/C function; specifically, gene ablation of CBP by RNA-mediated interference markedly reduces the E3 ubiquitin ligase activity of the APC/C and the progression of cells through mitosis. Taken together, our results define discrete roles for the APC/C-CBP/p300 complexes in growth regulation

On the Mechanics of Transcatheter Aortic Valve Replacement

Transcatheter aortic valves (TAVs) represent the latest advances in prosthetic heart valve technology. TAVs are truly transformational as they bring the benefit of heart valve replacement to patients that would otherwise not be operated on. Nevertheless, like any new device technology, the high expectations are dampened with growing concerns arising from frequent complications that develop in patients, indicating that the technology is far from being mature. Some of the most common complications that plague current TAV devices include malpositioning, crimp-induced leaflet damage, paravalvular leak, thrombosis, conduction abnormalities and prosthesis-patient mismatch. In this article, we provide an in-depth review of the current state-of-the-art pertaining the mechanics of TAVs while highlighting various studies guiding clinicians, regulatory agencies, and next-generation device designers