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Antigenically Active Nonhistone Chromatin Proteins in Cancer Cells¹

Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77025

Two-dimensional polyacrylamide gel electrophoresis shows that in nuclei of Novikoff hepatoma ascites cells there are approximately 75 proteins in the chromatin fraction soluble in 3 M NaCl:7 M urea. Dialysis of this fraction to an ionic strength of 0.15 produces a soluble fraction and a precipitate. The proteins in the soluble fraction have been reported to be active in gene control. Antibodies to the soluble fraction distribute diffusely throughout the nucleus, and antibodies to the precipitate localized primarily in the nucleolus and the nuclear ribonucleoprotein network. The nucleolar proteins differ from the extranucleolar proteins in antigenicity and labeling patterns.

The development of methods for isolation, purification, and identification of nuclear proteins provided the opportunity for analysis of chromatin antigens in tumor cells. Utilizing two-dimensional preparative polyacrylamide gel techniques as well as conventional procedures, several nuclear proteins have been isolated in electrophoretically homogeneous states including protein A-24, a histone-like nonhistone protein; C-14, a protein that stimulates nucleolar RNA polymerase; and a chromatin antigen soluble in 3 M NaCl:7 M urea that remains soluble after dialysis to 0.15 M NaCl to precipitate the histones and the DNA. This antigen has been found in the chromatin of both the Novikoff hepatoma and the Walker 256 carcinosarcoma but not in the chromatin of either normal or regenerating liver. It is a nonhistone nuclear protein as indicated by its amino acid analysis in which the ratio of the number of acidic to basic amino acids is approximately 1.4. Further studies are in progress on the function and structure of this chromatin protein. As an approach to analysis of relative rates of synthesis of this antigen and other proteins, the products of translation of messenger RNA of Novikoff hepatoma and normal liver are being analyzed by autoradiography of two-dimensional electrophoretic gels.

¹ Presented at the Symposium "Cancer and Chemistry" as part of the Fourth Conference on Embryonic and Fetal Antigens in Cancer, November 2 to 5, 1975, Charleston, S. C. These Studies were supported in part by the Cancer Center Grant CA-10893 awarded by the National Cancer Institute, DHEW, and by gifts from the Davidson Fund, the Wolff Memorial Foundation, and Mrs. Jack F. Hutchins.

² Presenter.

³ Postdoctoral Fellow supported by USPHS Training Grant CA-05154.