p53-mediated negative regulation of stathmin/Op18 expression is associatedwith G(2)/M cell-cycle arrest

Utilizing the technique of differential display of mRNA, we have identified p53-responsive genes that are transcriptionally up- or down-regulated as c ells enter growth arrest. One gene that was down-regulated, pong 16 was fou nd to be identical to stathmin/Op 18, a protein involved in the regulation of microtubule dynamics. Evidence that p53 is directly or indirectly involv ed in negative regulation of stathmin/Op 18 expression includes the followi ng: (i) p53-mediated growth inhibition is associated with repression of sta thmin/Op 18 expression following serum stimulation, (ii) reporter gene assa ys revealed p53-mediated repression of stathmin/Op 18 promoter activity and (iii) constitutive over-expression of stathmin/Op 18 bypasses a p53-mediat ed G(2)/M arrest in the cell cycle. These results suggest that p53-mediated negative regulation of stathmin/Op 18 plays an important role in cell-cycl e control. (C) 2000 Wiley-Liss, Inc.