E1A signaling to p53 involves the p19(ARF) tumor suppressor.
The adenovirus E1A oncogene activates p53 through a signaling pathway involving the retinoblastoma protein and the tumor suppressor p19(ARF). The ability of E1A to induce p53 and its transcriptional targets is severely compromised in ARF-null cells, which remain resistant to apoptosis following serum depletion or adriamycin treatment. Reintroduction of p19(ARF) restores p53 accumulation and resensitizes ARF-null cells to apoptotic signals. Therefore, p19(ARF) functions as part of a p53-dependent failsafe mechanism to counter uncontrolled proliferation. Synergistic effects between the p19(ARF) and DNA damage pathways in inducing p53 may contribute to E1A's ability to enhance radio- and chemosensitivity.
de Stanchina
E
E
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 USA.
McCurrach
M E
ME
Zindy
F
F
Shieh
S Y
SY
Ferbeyre
G
G
Samuelson
A V
AV
Prives
C
C
Roussel
M F
MF
Sherr
C J
CJ
Lowe
S W
SW
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D004249:DNA Damage; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D005814:Genes, Viral; D016158:Genes, p53; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics*; D015398:Signal Transduction; D025803:Tumor Suppressor Protein p14ARF
D017500:Adenovirus E1A Proteins; D011506:Proteins; D025803:Tumor Suppressor Protein p14ARF