title: Interaction with RXR is necessary for NPM-RAR-induced myeloid differentiation blockade.
abstract: The t(5;17)(q35;q21) APL variant results in expression of a fusion protein linking the N-terminus of nucleophosmin (NPM) to the C-terminus of the retinoic acid receptor alpha (RAR). We have previously shown that NPM-RAR is capable of binding to DNA either as a homodimer or heterodimer with RXR. To determine the biological significance of NPM-RAR/RXR interaction, we developed two mutants of NPM-RAR that showed markedly diminished ability to bind RXR. U937 subclones expressing the NPM-RAR mutants showed significantly less inhibition of vitamin D3/TGFbeta-induced differentiation, compared with NPM-RAR. These results support the hypothesis that RXR interaction is necessary for NPM-RAR-mediated myeloid maturation arrest.
authors.affiliation: Department of Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Rush
authors.forename: Sheri L
authors.initials: SL
authors.lastname: Pollock
authors.forename: Irina
authors.initials: I
authors.lastname: Abecassis
authors.forename: Robert L
authors.initials: RL
authors.lastname: Redner
mesh_terms: D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation; D002522:Chlorocebus aethiops; D015536:Down-Regulation; D006801:Humans; D022423:Myeloid Cells / Q000502:physiology*; D015514:Oncogene Proteins, Fusion / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D055503:Protein Multimerization / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors / Q000378:metabolism*; D020298:U937 Cells
chemical_list: C120276:NPM-RARalpha protein, human; D015514:Oncogene Proteins, Fusion; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors
keywords: Acute promyelocytic leukemia; Differentiation; NPM-RAR; RXR