PROLIFERATION-ASSOCIATED NUCLEAR ANTIGEN KI-S1 IS IDENTICAL WITH TOPOISOMERASE II-ALPHA - DELINEATION OF A CARBOXYL-TERMINAL EPITOPE WITH PEPTIDE ANTIBODIES

Proliferation-linked expression of the nuclear Ki-S1 antigen is a sign ificant prognostic indicator in mammary carcinomas. Here, we show stai ning of a Protein of 170 Ld by Ki-S1 antibody in immunoblots of Saccha romyces cerevisiae expressing human topoisomerase II alpha but not in the parental strain. In III-Go cells containing both isoforms of human topoisomerase II, Ki-SI antibody binds selectively to the 170-kd isoe nzyme in a similar fashion as peptide-antibodies directed against amin o acid residues 1 to 15 or 1512 to 1530 of human topoisomerase II alph a Conversely, antibodies directed against carboxyl-terminal sequences of human topoisomerase II beta selectively stahl a 180-kd protein. The immunoreactive pattern of V8 endoproteinase restriction digests of hu man topoisomerase II alpha was identical for Ki-S1-antibody and peptid e-antibodies directed against residues 1512 to 1530 but different for peptide-antibodies directed against residues 1 to 15. The R(f)values o f the smallest fragment commonly recognized by Ki-S1 antibody and the carboxy terminus-specific peptide-antibody place the Ki-S1 epitope wit hin the last 495 carboxyl-terminal amino acid residues of topoisomeras e II alpha.