Notch signaling plays a key role in the normal development of many tissues and cell types, through diverse effects on differentiation, survival, and/or proliferation that are highly dependent on signal strength and cellular context. Because perturbations in the regulation of differentiation, survival, and/or proliferation underlie malignant transformation, pathophysiologic Notch signals potenti...

Notch intercellular signaling is essential to cell fate decisions during differentiation, especially in stem cells and progenitor cells. It is also involved in controlling proliferation, survival, and homeostasis in many cell types. Notch signaling genes are targets for pathogenic mutations, including those associated with cancer. In the skeletal muscle lineage, Notch signaling is implicated in...

Notch signaling plays an important role during the development of different cell types and tissues. The role of Notch signaling in lymphocyte development, in particular in the development and commitment to the T cell lineage, has been the focus of research for many years. Notch signaling is absolutely required during the commitment and early stages of T cell development. Activation of the Notch...

Among other functions, the Notch signaling prevents the differentiation [4] of muscle progenitor cells into mature muscle in animals. The Notch signaling pathway is a pathway in animals by which two adjacent cells within an organism use a protein named Notch to mechanically interact with each other. Myogenesis is the formation of muscle that occurs throughout an animal's development, from embry...

The rostro-caudal polarity within a somite is primarily determined by the on/off state of Notch signaling, but the mechanism by which Notch is repressed has remained elusive. Here, we present genetic and biochemical evidence that the suppression of Notch signaling is essential for the establishment of rostro-caudal polarity within a somite and that Mesp2 acts as a novel negative regulator of th...

The Notch signaling pathway is a regulator of self-renewal and differentiation in several tissues and cell types. Notch is a binary cell-fate determinant, and its hyperactivation has been implicated as oncogenic in several cancers including breast cancer and T-cell acute lymphoblastic leukemia (T-ALL). Recently, several studies also unraveled tumor-suppressor roles for Notch signaling in differ...

BACKGROUND Notch and Wnt pathways are key regulators of intestinal homeostasis and alterations in these pathways may lead to the development of colorectal cancer (CRC). In CRC the Apc/β-catenin genes in the Wnt signaling pathway are frequently mutated and active Notch signaling contributes to tumorigenesis by keeping the epithelial cells in a proliferative state. These pathways are simultaneous...

Notch signaling is a conserved pathway of communication between neighboring cells that results in cell fate specification, and CSL is the universal transcriptional effector of Notch signaling. The Notch intracellular domain translocates to the nucleus after proteolytic release upon Notch extracellular engagement, and there it displaces corepressors from DNA-bound CSL and recruits activators of ...

Despite recent therapeutic advances, multiple myeloma (MM) is still an incurable neoplasia due to intrinsic or acquired resistance to therapy. Myeloma cell localization in the bone marrow milieu allows direct interactions between tumor cells and non-tumor bone marrow cells which promote neoplastic cell growth, survival, bone disease, acquisition of drug resistance and consequent relapse. Twenty...

Notch signaling is essential for the development of T cell progenitors through the interaction of NOTCH1 receptor on their surface with the ligand, Delta-like 4 (DLL4), which is expressed by the thymic epithelial cells. Notch signaling is quickly shut down once the cells pass β-selection, and CD4/CD8 double positive (DP) cells are unresponsive to Notch. Over the past two decades a number of pap...