Expression of the human DNA topoisomerase IIalpha (topo IIalpha) gene is positively regulated by the binding of the nuclear factor Y (NF-Y) transcription factor to four of five inverted CCAAT boxes (ICBs) located in its promoter. We have demonstrated previously that expression of the p53 tumor suppressor inhibits human topo IIalpha promoter activity in murine (10)1 cells. In this report, we dem...

DNA topoisomerase (topo) II modulates DNA topology and is essential for cell division. There are two isoforms of topo II (alpha and beta) that have limited functional redundancy, although their catalytic mechanisms appear the same. Using their COOH-terminal domains (CTDs) in yeast two-hybrid analysis, we have identified phospholipid scramblase 1 (PLSCR1) as a binding partner of both topo II alp...

Regulation of topoisomerase II (TOPO II) isozymes alpha and beta is influenced by the growth and transformation state of cells. Using HL-60 cells induced to differentiate by all-trans retinoic acid (RA), we have investigated the expression and regulation of TOPO II isozymes as well as the levels of topoisomerase I (TOPO I). During RA-induced differentiation of human leukemia HL-60 cells, levels...

DNA topoisomerase I (Topo I) specifically phosphorylates arginine-serine-rich (SR proteins) splicing factors and is potentially involved in pre-mRNA-splicing regulation. Using a Topo I-deficient murine B lymphoma-derived subclone (P388-45/C) selected for its resistance to high dosage of the antitumor drug camptothecin, we show that Topo I depletion results in the hypophosphorylation of SR prote...

A study of the distribution of Topoisomerase II alpha (Topo II) in cells of six tissue culture cell lines, human (HeLa), mouse (L929), rat, Indian muntjac, rat kangaroo (PTK-2), and wallaby revealed the following features: (1) There is a cell cycle association of a specific population of Topo II with the centromere. (2) The centromere is distinguished from the remainder of the chromosome by the...

Binding of simian virus 40 (SV40) large T antigen to human and calf thymus topoisomerase I (topo I) was readily detected by using modified enzyme-linked immunosorbent assays and immunoblots. In addition to WT T antigen, binding could also be readily demonstrated with T antigen fragments from the amino-terminal region as well as with fragments missing this region, but much less so with small t a...

Eukaryotic topoisomerase II (topo II) is the essential decatenase of newly replicated chromosomes and the main relaxase of nucleosomal DNA. Apart from these general tasks, topo II participates in more specialized functions. In mammals, topo IIα interacts with specific RNA polymerases and chromatin-remodeling complexes, whereas topo IIβ regulates developmental genes in conjunction with chromatin...

P-glycoprotein (P-gp) expression and DNA topoisomerase (Topo) II are important variables in multidrug resistant tumor cell lines. The aim of this study was to evaluate P-gp expression and Topo I and II activity in benign and malignant epithelial ovarian tumors. P-gp expression was analyzed immunohistochemically in cryostat sections of fresh tumor specimens. In the same specimens Topo I and II a...

14-Ethyl-2,5,11-trimethyl-4,13,19,20-tetraoxa-tricyclo[14.2.1.1(7,10)]eicosane-3,12-dione (MFTZ-1), a new macrolide compound isolated from Streptomyces sp. Is9131, displayed wide cytotoxicity in human tumor cell lines with an average IC(50) of 0.905 micromol/L. Notably, MFTZ-1 showed significant cytotoxicity in the three multidrug resistance cell lines with an average resistance factor of 2.08....

The outer cells of Chinese hamster V79 spheroids are about 10 times more resistant than monolayers to DNA damage and cell killing by the topoisomerase (topo) II inhibitor etoposide. Although the amount and catalytic activity of topo IIalpha are identical for monolayers or the outer cells of spheroids, and the cell proliferation rate is the same, our previous results indicated that phosphorylati...