Commitment to erythroid differentiation in mouse erythroleukemia cells is controlled by alterations in topoisomerase IIα phosphorylation
Date
1996Source
Cancer researchVolume
56Pages
4192-4199Google Scholar check
Keyword(s):
Metadata
Show full item recordAbstract
To explore the program of cell differentiation in Friend murine erythroleukemia (MEL) cells, we used three clonal variants: phorbol 12- myristate 13-acetate (PMA)-hypersensitive TS-19-101, PMA-resistant TR19-9, and hexamethylene bis-acetamide (HMBA)- and PMA-resistant DS19/R1. After treating TS19-101 cells with HMBA, topoisomerase II (topo II) enzymatic activity was dramatically reduced, and cells became terminally differentiated. The initial reduction in activity was soon followed by reduced topo IIα phosphorylation, but only later did the protein level drop significantly. PMA, which completely blocked HMBA-induced differentiation in TS19-101 cells, increased the phosphorylation of topo IIα and restored the enzymatic activity to its original levels. Reduced topo II activity and phosphorylation were also evident in HMBA-treated TR19-9 cells. PMA failed to restore topo II activity and phosphorylation to their original levels in TR19-9 cells. Predictably, the topo II activity and phosphorylation of DS19/R1 cells showed little change in response to HMBA or PMA treatment. Structural changes in chromatin became evident in sensitive cells 24 h after HMBA treatment, suggesting that alterations in topo IIα phosphorylation may control cell differentiation by altering nuclear architecture.
Collections
Cite as
Related items
Showing items related by title, author, creator and subject.
-
Article
Selection of cancer chemopreventive agents based on inhibition of topoisomerase II activity
Cho, K. H.; Pezzuto, J. M.; Bolton, J. L.; Steele, V. E.; Kelloff, G. J.; Lee, S. K.; Constantinou, Andreas I. (2000)The present study was undertaken to determine if in vitro inhibition of one or both of the two most dominant mammalian DNA topoisomerases (topos) is common among chemopreventive agents. To determine if an agent was a topo ...
-
Article
Flavonoids as DNA topoisomerase antagonists and poisons: Structure-activity relationships
Constantinou, Andreas I.; Mehta, R.; Runyan, C.; Rao, K.; Vaughan, A.; Moon, R. (1995)Selected flavonoids were tested for their ability to inhibit the catalytic activity of DNA topoisomerase (topo) I and II. Myricetin, quercetin, fisetin, and morin were found to inhibit both enzymes, while phloretin, ...
-
Article
Inhibition of topoisomerase IIα activity in CHO K1 cells by 2- [(aminopropyl)amino]ethanethiol (WR-1065)
Grdina, D. J.; Constantinou, Andreas I.; Shigematsu, N.; Murley, J. S. (1994)The aminothiol 2-[(aminopropyl)amino]ethanethiol (WR-1065) is the active thiol of the clinically studied radioprotective agent S-2-(3- aminopropylamino)ethylphosphorothioic acid (WR-2721). WR-1065 is an effective radiation ...