Protein phosphorylation and dephosphorylation has been recognized as a key mechanism in cell proliferation, differentiation, and apoptosis in various tissues. Okadaic acid is a potent inhibitor of protein phosphatase type 1 (PP1) and type 2A and induces apoptosis in human osteoblastic Saos-2 and MG63 cells. Nucleolin is an abundantly expressed nucleolar phosphoprotein and is located mainly in the nucleolus. The staining pattern of nucleolin in Saos-2 and MG63 cells is similar to that of PP1 delta. Nucleolin was demonstrated to bind to PP1 delta in nucleolus by using immunocytochemical and immunoprecipitation methods. AgNORs and nucleolin, visible as dots in the nucleus of the control cells, disappeared from the apoptotic nuclei. A major band, 110 kDa, was detected in the proteins obtained from the control cells. The level of the 110 kDa protein decreased in the apoptotic cells, whereas an additional band, 80 kDa, appeared and the level of this protein increased in the proteins prepared from okadaic acid-induced apoptotic cells. Our results indicate that PP1 delta directly binds to nucleolin in the nucleolus and that nucleolin is cleaved during apoptosis.