p21 (Waf1/Cip1) and FasL gene activation via Sp1 and NFκB is required for leukemia cell survival but not for cell death induced by diverse stimuli
2005 (English)In: International Journal of Biochemistry and Cell Biology, ISSN 1357-2725, Vol. 37, no 4, 784-796 p.Article in journal (Refereed) Published
The molecular mechanisms of the cellular response to different apoptotic effectors are only partially understood. Herein, the role of transcription factors, Sp1 and NFκB in differentiation-related and etoposide-induced apoptosis was examined in a number of human leukemia cell lines (HL-60, NB4, HEL, THP-1, K562). This was investigated with respect to the recruitment of one cell-cycle regulating gene, p21 and one cell death gene, FasL. Using electrophoretic mobility shift assay (EMSA), we consistently observed Sp1 and NFκB binding activity to the promoter of either gene during cell differentiation and the decrease associated with apoptosis upon long-term treatment with differentiation inducers in HL-60, NB4 and HEL cells. By contrast, Sp1 and NFκB binding capacities were lost in all myeloid cell lines undergoing etoposide-induced fast apoptosis. This effect was eliminated by the broad-spectrum caspase inhibitor, benzyloxycarbonyl-valinyl-alaninyl- aspartyl fluoromethylketone, thus restoring transcription factors' binding activity. However, sustained NFκB binding to the FasL promoter was noticed in apoptosis undergoing HEL cells treated by etoposide. Our results suggest that p21 and FasL gene activation is required for myeloid leukemia cell survival or maturation but not for cell death via Sp1 and NFκB as regulators of these genes. The findings also support the idea of a common mechanism for cellular responses to different apoptotic effectors in malignant hematopoietic cell lines. © 2004 Elsevier Ltd. All rights reserved.
Place, publisher, year, edition, pages
2005. Vol. 37, no 4, 784-796 p.
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-24660DOI: 10.1016/j.biocel.2004.10.002Local ID: 6890OAI: oai:DiVA.org:liu-24660DiVA: diva2:244982