ABSTRACT
DREAM (downstream regulatory element antagonist modulator), Calsenilin and KChIP3 (potassium channel interacting protein 3) belong to the neuronal calcium sensor (NCS) superfamily, which transduces the intracellular calcium signaling into a variety of activities. They are encoded by the same gene locus, but have distinct subcellular locations. DREAM was first found to interact with DRE (downstream regulatory element) site in the vicinity of the promoter of prodynorphin gene to suppress gene transcription. Calcium can disassemble this interaction by binding reversibly to DREAM protein on its four EF-hand motifs. Apart from having calcium dependent DRE site binding, DREAM can also interact with other transcription factors, such as cAMP responsive element binding protein (CREB), CREB-binding protein (CBP) and cAMP responsive element modulator (CREM), by this concerted actions, DREAM extends the gene pool under its control. DREAM is predominantly expressed in central nervous system with its highest level in cerebellum, and accumulating evidence demonstrated that DREAM might play important roles in pain sensitivity. Novel findings have shown that DREAM is also involved in learning and memory processes, Alzheimer's disease and stroke. This mini-review provides a brief introduction of its discovery history and protein structure properties, focusing on the mechanism of DREAM nuclear translocation and gene transcription regulation functions.
Subject(s)
Gene Expression Regulation , Kv Channel-Interacting Proteins/physiology , Repressor Proteins/physiology , Animals , Calcium Signaling/physiology , Humans , Kv Channel-Interacting Proteins/genetics , Pain Threshold , Repressor Proteins/geneticsABSTRACT
Cell migration is identified as a highly orchestrated process. It is a fundamental and essential phenomenon underlying tissue morphogenesis, wound healing, and immune response. Under dysregulation, it contributes to cancer metastasis. Brain is considered to be the most complex organ in human body containing many types of neural cells with astrocytes playing crucial roles in monitoring both physiological and pathological functions. Astrocytoma originates from astrocytes and its most malignant type is glioblastoma multiforme (WHO Grade IV astrocytoma), which is capable to infiltrate widely into the neighboring brain tissues making a complete resection of tumors impossible. Very recently, we have reviewed the mechanisms for astrocytes in migration. Given the fact that astrocytoma shares many histological features with astrocytes, we therefore attempt to review the mechanisms for glioma cells in migration and compare them to normal astrocytes, hoping to obtain a better insight into the dysregulation of migratory mechanisms contributing to their metastasis in the brain.
