Identification of apoptotic tyrosine-phosphorylated proteins after etoposide or retinoic acid treatment of HL-60 cells
2004 (English)In: Proteomics, ISSN 1615-9853, Vol. 4, no 4, 1029-1041 p.Article in journal (Refereed) Published
A main shortcoming of using HL-60 cells as a model of granulocyte-macrophage differentiation is that some cells in the differentiating population undergo apoptosis. To address this issue, we have identified which tyrosine-phosphorylated proteins are involved in apoptosis and differentiation, respectively. HL-60 cells were induced specifically to undergo apoptosis with 68 µM etoposide, and to undergo granulocytic differentiation with 1 µM retinoic acid (RA). The corresponding two-dimensional electrophoretic maps of tyrosine-phosphorylated proteins from treated cells were compared. In the 8 h etoposide-treated HL-60 cell population, 83% of the cells were apoptotic. In the 120 h RA-treated cells, 50% of the cells were apoptotic. Eighteen cytosolic and nuclear tyrosine-phosphorylated proteins were found in both the 8 h etoposide- and the 120 h RA-treated cells, but not in the proliferating HL-60 cell population. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry analyses suggested that some of the proteins may be involved in signal transduction pathways (NF?B, GTP-binding protein, protein disulfide isomerase, Cyclophilin A), others in cell transcriptional and translational control (hnRNP H, hnRNP L, Hsp60, Hp1, Hcc-1, 26S proteasome beta-subunit, ATP synthase beta-chain), and a third group in cell cytoskeleton organization and receptor cycling (profilin, caveolin-1). An understanding of signal transduction in apoptosis initiation by screening for tyrosine-phosphorylated proteins associated with apoptosis may provide new targets for the treatment of leukemia.
Place, publisher, year, edition, pages
2004. Vol. 4, no 4, 1029-1041 p.
Apoptosis, Differentiation, Etoposide, Tyrosine phosphorylation
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-45783DOI: 10.1002/pmic.200300671OAI: oai:DiVA.org:liu-45783DiVA: diva2:266679