期刊
EXPERIMENTAL CELL RESEARCH
卷 315, 期 13, 页码 2241-2248出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2009.03.004
关键词
Nuclear Raf1; All trans-retinoic acid; Leukemia; HL-60
资金
- USPHS NIH [CA33505]
- NYSTEM
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. (C) 2009 Elsevier Inc. All rights reserved.
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