Nuclear uptake of monoclonal antibody to a surface glycoprotein and its effect on transcription

Nuclear transport and chromatin binding of monoclonal antibody (MAb) ME491, directed against a cell surface glycoprotein, was tested in intact cells and in a cell-free system. After a 24-h incubation with 125I-MAb ME491, the chromatin of melanoma cells and of colorectal carcinoma cells contained approximately 10 and 20%, respectively, of the antibody in nondegraded form. 125I-MAb ME491 was bound to a 55-kDa chromatin protein and localized in two HincII-digested chromatin fragments. Taken up by the nucleus, MAb ME491 inhibited transcription of ribosomal RNA genes by 70%. Nuclear uptake of 125I-MAb ME491 was increased up to ninefold when cells were preincubated with puromycin or actinomycin D. Nuclear uptake of MAb ME491 in a cell-free system was inhibited by ME491 antigen newly synthesized in the cytoplasm. Binding of 125I-MAb ME491 to the newly synthesized ME491 antigen caused precipitation of polysome-bound ME491 mRNA. The effect of MAb ME491 on transcription is discussed.