We rely on insulin supplied by our pancreas at the right dose and at the right time to control our blood glucose levels and energy storage. Insulin works by regulating the energy usage of various cell types in the body. When this process goes awry, it can cause diabetes.
There are two types of diabetes, defined by how insulin is
dysregulated. In Type 1 Diabetes (T1D), the pancreas produces too little
insulin. Patients need to give themselves insulin in order to respond to
glucose in the diet. In Type 2 Diabetes (T2D), patients do not respond well to
the insulin produced in their body. Therefore, they need to give themselves
more to avoid hyperglycemia (high blood glucose).
Ubiquitin modification of a protein directs events such as targeting for proteasomal degradation. Targeting a protein for degradation through ubiquitin modification is one way to regulate the amount of time a signaling protein, such as a kinase or other enzyme, is available to participate in cell signaling events. Deubiquitinases (DUBs) are enzymes that cleave the ubiquitin tags from proteins, and they have been implicated in several diseases, including cancer.
With their roles in the stabilization of proteins involved in cell cycle progression and other critical processes, DUBs are promising targets for small molecule inhibitors, particularly since they may provide a “back door” for targeting otherwise intractable, undruggable proteins by modulating their half lives. However, finding small molecule inhibitors of the ubiquitin proteases to date has not been trivial. Here we highlight two papers describing the identification and characterization of small molecule inhibitors against the DUB USP7. Continue reading “Deubiquitinases: A Backdoor into Undruggable Targets?”
A quick search of the PubMed database for “dual luciferase” quickly returns over 1,000 papers. The Dual-Luciferase® Reporter Assay is a powerful tool that allows researchers to ask a multitude of questions about gene control and expression in a system that itself could be normalized and internally controlled. For more than 15 years, firefly and Renilla luciferases have formed the basis of a range of powerful assays and research tools for scientists who are asking questions about the deep and complex genetic and cellular story associated with cancer. Here we talk a bit of about bioluminescent chemistries, some of the newest bioluminescent tools available, and how some of these tools can be used to probe the deeper questions of cell biology, including cancer biology. Continue reading “Shining a Bright Light on Deep Questions in Biology with Bioluminescence”
For those of us entering the world of cell-based assays from a classical or molecular genetics background, the world of cell culture can be daunting. Yet to truly understand how the genetic mutation behind a particular phenotype works, we need to look at the biochemistry and cell biology where it all occurs: the cell.