p53-mediated negative regulation of stathmin/Op18 expression is associated with 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 cells enter growth arrest. One gene that was down-regulated, pong16, was found to be identical to stathmin/Op18, a protein involved in the regulation of microtubule dynamics. Evidence that p53 is directly or indirectly involved in negative regulation of stathmin/Op18 expression includes the following: (i) p53-mediated growth inhibition is associated with repression of stathmin/Op18 expression following serum stimulation, (ii) reporter gene assays revealed p53-mediated repression of stathmin/Op18 promoter activity and (iii) constitutive over-expression of stathmin/Op18 bypasses a p53-mediated G(2)/M arrest in the cell cycle. These results suggest that p53-mediated negative regulation of stathmin/Op18 plays an important role in cell-cycle control.
Johnsen
J I
JI
Department of Virology, Faculty of Medicine, University of Tromso, Tromso Norway.
Aurelio
O N
ON
Kwaja
Z
Z
Jörgensen
G E
GE
Pellegata
N S
NS
Plattner
R
R
Stanbridge
E J
EJ
Cajot
J F
JF
D015536:Down-Regulation; D016195:G2 Phase / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008868:Microtubule Proteins; D008938:Mitosis / Q000502:physiology*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D050777:Stathmin; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D008868:Microtubule Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C493995:STMN1 protein, human; D050777:Stathmin; D016159:Tumor Suppressor Protein p53