THE AGE-DEPENDENT BINDING OF CBP TK, A CCAAT BINDING-PROTEIN, IS DEREGULATED IN TRANSFORMED AND IMMORTALIZED MAMMALIAN-CELLS BUT ABSENT IN PREMATURE AGING CELLS/

CBP/tk, CCAAT Binding Protein for thymidine kinase, has been shown to bind to the distal and proximal CCAAT elements in human TK gene at GI/ S boundary in normal human IMR-90 cells after serum stimulation (Pang and Chen, 1993), We now show that the serum-induced binding activity o f CBP/tk was inversely related to the population doubling level (PDL) of the normal IMR-90 cells. However, little or almost no CBP/tk bindin g activity was observed in cells derived from patients with premature aging syndromes (e.g., Werner, Hutchinson-Gilford, and Cockayne syndro me). In contrast, CBP/tk binding activity in SV-40 virus-transformed h uman cells and in HeLa cells was overexpressed at levels 5- to 15-fold higher than that in normal cells and appeared to be deregulated, The half-life of CBP/tk binding activity in SV-40 transformed cells was at least 10 times longer than that in normal IMR-90 cells, suggesting th at posttranslational control may contribute to the deregualtion. CBP/t k binding activity detected in other mammalian cells such as murine NI H3T3, an immortal cell line, did not reveal any cell cycle dependence either. Further characterization of CBP/tk binding complex indicates t hat the binding complex may contain NF-YA and NF-YB and that the bindi ng activity was sensitive to oxidizing reagents. Taken together, our d ata showed that the age- and cell cycle-dependent nature of CBP/tk is a function of cell types and that CBP/tk binding activity may be subje cted to posttranslational and redox regulation.