Regulation of C/EBP{beta} isoforms by MAPK pathways in HL60 cells induced to differentiate by 1,25-dihydroxyvitamin D{sub 3}

Journal Article · Sat Jul 01 00:00:00 EDT 2006 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2006.03.003· OSTI ID:20857994

Marcinkowska, Ewa ^[1]; Garay, Edward ^[2]; Gocek, Elzbieta ^[1]; Chrobak, Agnieszka ^[3]; Wang, Xuening ^[2]; Studzinski, George P ^[2]

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1. Institute of Biochemistry and Molecular Biology, University of Wroclaw, Tamka 2, 50-137 Wroclaw (Poland)
2. Department of Pathology and Laboratory Medicine, UMDNJ-New Jersey Medical School, Newark, NJ 07103 (United States)
3. Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolf Weigl St. 12, 53-114 Wroclaw (Poland)

C/EBP{beta} is known to be important for monocytic differentiation and macrophage function. Here, we found that expression of all three C/EBP{beta} isoforms induced in HL60 cells by 1,25-dihydroxyvitamin D{sub 3} (1,25D) was upregulated in a sustained manner that correlates with the appearance of monocytic phenotype and with the G1 phase cell cycle arrest. In 1,25D-resistant HL60-40AF cells, isoforms {beta}-1 and {beta}-3 were expressed at levels comparable to 1,25D-sensitive HL60-G cells, but isoform {beta}-2 was difficult to detect. Treatment of sensitive HL60 cells with 1,25D resulted in predominantly nuclear localization of C/EBP isoforms {beta}-2 and {beta}-3, while a large proportion of C/EBP{beta}-1 remained in the cytoplasm. Attenuation of the MEK-ERK MAPK pathway by the inhibitor PD98059 markedly reduced the expression, 1,25D-induced phosphorylation and nuclear localization of C/EBP{beta}-2 and C/EBP{beta}-3. Interestingly, only the lower molecular mass isoforms of C/EBP{beta} phosphorylated on Thr235 were found in the nuclei, while C/EBP{beta}-1 was constitutively phosphorylated and was detected principally in the cytoplasmic fraction. Although the role of C/EBP{beta} isoforms in 1,25D-induced differentiation is complex, our results taken together strongly suggest that the phosphorylation of C/EBP{beta} isoforms on Thr235 takes place mainly via the MEK-ERK pathway and that C/EBP{beta}-2 is the principal transcription factor in this cell system.

• OSTI ID: 20857994
• Journal Information: Experimental Cell Research, Vol. 312, Issue 11; Other Information: DOI: 10.1016/j.yexcr.2006.03.003; PII: S0014-4827(06)00091-7; Copyright (c) 2006 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
ATTENUATION
CELL CYCLE
CYTOPLASM
GENE REGULATION
MACROPHAGES
PHENOTYPE
PHOSPHORYLATION
TRANSCRIPTION FACTORS
VITAMIN D