Transcriptional and post-transcriptional regulation of pr22 (Op18) with proliferation control.
The pr22 gene was isolated as a gene which is expressed in proliferating cells but not in cells which are differentiated or growth-arrested. When cells of the human monocytic cell line, U937, were differentiated into macrophages, transcription of pr22 was almost completely suppressed. Serum starvation resulted in the inhibition of transcription, although U937 failed to differentiate. In a culture synchronized with excess thymidine, mRNA of pr22 was detected at the G1/S boundary, with the level increasing in the S phase and decreasing in the G2 phase. The gene product, pr22 protein (Pr22) was found to be identical to Op18 as well as to a catastrophe factor. Genes homologous to pr22 were detected in the genome of mouse but not in that of yeast, or Drosophila. The 5' up-stream region of the genomic pr22 contained CpG islands but no TATA box at its appropriate position. About 20% of cell nuclei of normal human fibroblasts were stained in a speckled manner with a monoclonal antibody for C-terminal peptide of Pr22, and these cells were found to be in phases S and G2. The mitotic apparatus was also strongly stained. By Western blot analysis, Pr22 was detected in the nuclear fraction but not in the cytoplasm. The level increased from middle S to G2 phase and remained high until the early G1 phase. N-terminal truncated Pr22 was also detected in these phases. These results suggest that Pr22 may have an additional role other than just functioning in association with microtubules.