Retinoic acid induces nuclear accumulation of Raf1 during differentiation of HL-60 cells

Journal Article · Sat Aug 01 00:00:00 EDT 2009 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2009.03.004· OSTI ID:22209786

Smith, James; Bunaciu, Rodica P.; Reiterer, Gudrun ^[1]; Coder, David; George, Thaddeus ^[2]; Asaly, Michael ^[1]; Yen, Andrew ^[1]

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1. Department of Biomedical Sciences, T4-008 VRT, Cornell University, Ithaca, NY 14853 (United States)
2. Amnis Corporation, Seattle, Washington (United States)

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.

• OSTI ID: 22209786
• Journal Information: Experimental Cell Research, Vol. 315, Issue 13; Other Information: Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
DRUGS
LEUKEMIA
METABOLITES
PHOSPHORYLATION
RECEPTORS
RETINOIC ACID
SERINE
THERAPY