title: Retinoic acid induces nuclear accumulation of Raf1 during differentiation of HL-60 cells.
abstract: All trans-retinoic acid (RA) is a standard therapeutic agent used in differentiation induction therapy treatment of acute promyelocytic leukemia (APL). RA and its metabolites use a diverse set of signal transduction pathways during the differentiation program. In addition to the direct transcriptional targets of the nuclear RAR and RXR receptors, signals derived from membrane receptors and the Raf-MEK-ERK pathway are required. Raf1 phosphorylation and the prolonged activation of Raf1 persisting during the entire differentiation process are required for RA-dependent differentiation of HL-60 cells. Here we identify a nuclear redistribution of Raf1 during the RA-induced differentiation of HL-60 cells. In addition, the nuclear accumulation of Raf1 correlates with an increase in Raf1 phosphorylated at serine 621. The serine 621 phosphorylated Raf1 is predominantly localized in the nucleus. The RA-dependent nuclear accumulation of Raf1 suggests a novel nuclear role for Raf1 during the differentiation process.
authors.affiliation: Department of Biomedical Sciences, T4-008 VRT, Cornell University, Ithaca, NY 14853, USA.
authors.forename: James
authors.initials: J
authors.lastname: Smith
authors.forename: Rodica P
authors.initials: RP
authors.lastname: Bunaciu
authors.forename: Gudrun
authors.initials: G
authors.lastname: Reiterer
authors.forename: David
authors.initials: D
authors.lastname: Coder
authors.forename: Thaddeus
authors.initials: T
authors.lastname: George
authors.forename: Michael
authors.initials: M
authors.lastname: Asaly
authors.forename: Andrew
authors.initials: A
authors.lastname: Yen
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism*; D018922:HL-60 Cells / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: C520537:1,5-bis((2-(methylamino)ethyl)amino)-4,8-dihydroxyanthracene-9,10-dione; D000880:Anthraquinones; D000970:Antineoplastic Agents; D012694:Serine; D014212:Tretinoin; D019908:Proto-Oncogene Proteins c-raf