JAK-STAT signaling involved in phorbol 12-myristate 13-acetate- and dimethyl sulfoxide-induced 2′-5′ oligoadenylate synthetase expression in human HL-60 leukemia cells

Shenhav Cohen, Sara Dovrat, Ronit Sarid, Eliezer Huberman, Samuel Salzberg

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The JAK-STAT signal transduction cascade participates in various cellular processes, including immune response, cell replication, differentiation and oncogenesis. Here, we report that this cascade is induced in two human myeloid HL-60 leukemia cell variants by the granulocyte differentiation inducer dimethyl sulfoxide (DMSO) and macrophage differentiation inducer phorbol 12-myristate 13-acetate (PMA). DMSO and PMA also induced the expression and catalytic activity of 2′-5′ oligoadenylate synthetase (2-5A synthetase), a known interferon (IFN) inducible enzyme. The HL-60 cell variants included HL-205, which is susceptible to DMSO- and PMA-induced differentiation, and HL-525, which is susceptible to DMSO- but not to PMA-induced differentiation. Treatment of HL-205 and HL-525 cells with DMSO and HL-205 cells with PMA-induced JAK1 phosphorylation, JAK1/STAT1 association, formation of STAT1-STAT2 heterodimers, and the binding of the active IFN stimulating growth factor 3 (ISGF3) to the IFN-stimulated response element (ISRE) fragment isolated from the 2-5A synthetase promoter. These events were either reduced or absent in the resistant HL-525 cells treated with PMA. Taken together, our data implicate the above signaling cascade in DMSO- and PMA-induced 2-5A synthetase expression and catalytic activity in the HL-60 cell system.

Original languageEnglish
Pages (from-to)923-931
Number of pages9
JournalLeukemia Research
Volume29
Issue number8
DOIs
StatePublished - Aug 2005

Bibliographical note

Funding Information:
This research was supported by the National Institutes of Health: Grant No. CA80826 to E.H.

Funding

This research was supported by the National Institutes of Health: Grant No. CA80826 to E.H.

FundersFunder number
National Institutes of Health
National Cancer InstituteR01CA080826

    Keywords

    • 2′-5′ Oligoadenylate synthetase
    • DMSO
    • Differentiation
    • HL-60
    • Interferon stimulated response element
    • Interferon-stimulated gene factor complex
    • JAK/STAT signaling
    • PMA
    • Protein kinase C
    • STAT1
    • STAT2

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