Nuclear localization of bacterial Streptoalloteichus hindustanus bleomycin resistance protein in mammalian cells

TP Calmels, JS Mistry, SC Watkins, PD Robbins, R McGuire and JS Lazo

Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania 15261.

Prokaryotes produce a variety of toxins that affect genomic function of both eukaryotes and prokaryotes. The 375-base pair bacterial gene Streptoalloteichus hindustanus (Sh) ble encodes a small protein, Streptoalloteichus hindustanus bleomycin resistance protein (BRP), that inhibits in vitro DNA cleavage by the prokaryotic glycopeptide bleomycin, which is a clinically used anticancer drug. NIH/3T3 cells infected with a retroviral vector containing Sh ble (SH-9 cells) were highly resistant to the cytotoxicity of bleomycin-like drugs but not to the cytotoxicity of other, structurally unrelated, DNA-cleaving agents. Expression of BRP did not markedly alter total cellular content or distribution of bleomycin-like compounds. Fluorescently labeled bleomycin was primarily localized in cytoplasmic vesicles in NIH/3T3 and SH-9 cells, whereas BRP, which has no established nuclear localization sequence, was segregated to the nucleus and more specifically to euchromatin. This karyophilic BRP may intercept bleomycin in the nucleus.

Volume 44, Issue 6, pp. 1135-1141, 12/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics

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