p53 is involved in the p120E4F-mediated growth arrest.
Control of cell growth and division by the p53 tumor suppressor protein requires its abilities to transactivate and repress specific target genes and to associate in complex with other proteins. Here we demonstrate that p53 binds to the E1A-regulated transcription factor p120E4F, a transcriptional repressor of the adenovirus E4 promoter. The interaction involves carboxy-terminal half of p120E4F and sequences located at the end of the sequence-specific DNA-binding domain of p53. Ectopic expression of p120E4F leads to a block of cell proliferation in several human and murine cell lines and this effect requires the association with wild-type (wt) p53. Although p120E4F can also bind to mutant p53, the growth suppression induced by overexpression of the protein is severely reduced in a cell line that contains mutant p53. These data suggest that p120E4F may represent an important element within the complex network of p53 checkpoint functions.
Sandy
P
P
Laboratorio Nazionale, Consorzio Interuniversitario Biotecnologie, AREA Science Park, Padriciano 99, 34012 Trieste, Italy.
Gostissa
M
M
Fogal
V
V
Cecco
L D
LD
Szalay
K
K
Rooney
R J
RJ
Schneider
C
C
Del Sal
G
G
D016475:3T3 Cells; D017504:Adenovirus E4 Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D000596:Amino Acids / Q000502:physiology; D000818:Animals; D006131:Growth Inhibitors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000502:physiology; D011485:Protein Binding / Q000235:genetics; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology
D017504:Adenovirus E4 Proteins; D000596:Amino Acids; D006131:Growth Inhibitors; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53