title: Linking Notch signaling, chromatin remodeling, and T-cell leukemogenesis.
abstract: Intercellular communication that controls the developmental fate of multipotent cells is commonly mediated by the Notch family of transmembrane receptors. Specific transmembrane ligands activate Notch receptors on neighboring cells inducing the proteolytic liberation and nuclear translocation of the intracellular domain of Notch (N(IC)). Nuclear N(IC) associates with a transcriptional repressor known as C-promoter binding factor/RBP-J kappa, suppressor of hairless, or LAG-1, converting it from a repressor into an activator. Through physical interactions with chromatin remodeling enzymes and potentially with components of the transcriptional machinery, N(IC) activates target genes that mediate cell fate decisions. As Notch1 is disrupted via a chromosomal translocation in a subset of human T-cell leukemia, leading to a truncated polypeptide resembling N(IC), deregulated chromatin remodeling and transcription may fuel uncontrolled cell proliferation in this hematopoietic malignancy. This review summarizes the mechanics of Notch signaling and focuses on prospective molecular mechanisms for how constitutively active Notch might derail nuclear processes as an initiating step in T-cell leukemogenesis. J. Cell. Biochem. Suppl. 35:46-53, 2000.
authors.affiliation: Department of Pharmacology, University of Wisconsin Medical School, 1300 University Avenue, Madison, WI 53706, USA. ehbresni@facstaff.wisc.edu
authors.forename: E H
authors.initials: EH
authors.lastname: Bresnick
authors.forename: J
authors.initials: J
authors.lastname: Chu
authors.forename: H M
authors.initials: HM
authors.lastname: Christensen
authors.forename: B
authors.initials: B
authors.lastname: Lin
authors.forename: J
authors.initials: J
authors.lastname: Norton
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D006801:Humans; D015458:Leukemia, T-Cell / Q000209:etiology* / Q000378:metabolism*; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D051880:Receptors, Notch; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D008024:Ligands; D008565:Membrane Proteins; D051880:Receptors, Notch