CRHR1 endocytosis: Spatiotemporal regulation of receptor signaling.

Corticotropin releasing hormone (CRH) is crucial for basal and stress-initiated reactions in the hypothalamic-pituitary-adrenal axis (HPA) and extrahypothalamic brain circuits, where it acts as a neuromodulator to organize behavioral and humoral responses to stress. We review and describe cellular components and molecular mechanisms involved in CRH system signaling through G protein-coupled receptors (GPCRs) CRHR1 and CRHR2, under the current view of GPCR signaling from the plasma membrane but also from intracellular compartments, which establish the bases of signal resolution in space and time. Focus is placed on latest studies of CRHR1 signaling in physiologically significant contexts of the neurohormone function that disclosed new mechanistic features of cAMP production and ERK1/2 activation.

Glucocorticoids uncover a critical role for ASH2L on BCL-X expression regulation in leukemia cells.

Targeting the apoptosis machinery is a promising therapeutic approach in myeloid malignancies. BCL2L1 is a well-known glucocorticoid-responsive gene and a key apoptosis regulator that, when over-expressed, can contribute to tumor development, progression and therapeutic resistance. Moreover, synthetic glucocorticoids, like dexamethasone, are frequently used in the treatment of hematopoietic diseases due to its pro-apoptotic properties.