Combined carotid endarterectomy and transcatheter aortic valve replacement: Technique and outcomes.

Background: Stroke and transient ischemic attack after transcatheter aortic valve replacement results in significantly higher morbidity and mortality. Severe carotid artery disease may be a contributing factor to this increased risk. We report our technique and outcomes of combined carotid endarterectomy (CEA) with transcatheter aortic valve replacement (TAVR).

The emerging role of deubiquitinating enzymes in genomic integrity, diseases, and therapeutics.

The addition of mono-ubiquitin or poly-ubiquitin chain to signaling proteins in response to DNA damage signal is thought to be a critical event that facilitates the recognition of DNA damage lesion site, the activation of checkpoint function, termination and checkpoint response and the recruitment of DNA repair proteins. Despite the ubiquitin modifiers, removal of ubiquitin from the functional proteins by the deubiquitinating enzymes (DUBs) plays an important role in orchestrating DNA damage response as well as DNA repair processes. Deregulated ubiquitination and deubiquitination could lead to genome instability that in turn causes tumorigenesis.

Insights into APC/C: from cellular function to diseases and therapeutics.

Anaphase-promoting complex/cyclosome (APC/C) is a multifunctional ubiquitin-protein ligase that targets different substrates for ubiquitylation and therefore regulates a variety of cellular processes such as cell division, differentiation, genome stability, energy metabolism, cell death, autophagy as well as carcinogenesis. Activity of APC/C is principally governed by two WD-40 domain proteins, Cdc20 and Cdh1, in and beyond cell cycle. In the past decade, the results based on numerous biochemical, 3D structural, mouse genetic and small molecule inhibitor studies have largely attracted our attention into the emerging role of APC/C and its regulation in biological function, human diseases and potential therapeutics.

New insights into posttranslational modifications of Hippo pathway in carcinogenesis and therapeutics.

PTMs (posttranslational modifications) such as ubiquitylation, sumoylation, acetylation and protein methylation are pivotal modifiers that determine the activation, deactivation or subcellular localization of signaling proteins, facilitating the initiation, amplification and transduction of signaling. Accumulating evidence suggest that several key signaling molecules in Hippo signaling pathway are tightly regulated by various types of PTMs. Malfunction of these critical signaling modules such as YAP/TAZ, MAT1/2 and LATS1/2 due to deregulated PTMs has been linked to a variety of human diseases such as cancer.