Association of p14ARF with the p120E4F transcriptional repressor enhances cell cycle inhibition.
The p14(ARF) tumor suppressor is a key regulator of cellular proliferation and is frequently inactivated in human cancer. This tumor suppressor functions in the p53 and pRb cell cycle regulatory pathways and can effectively activate both pathways to induce growth arrest or cell death. We now report that p14(ARF) forms a complex with the E1A-regulated transcriptional repressor, p120(E4F). p120(E4F) contacts p14(ARF) and p53 to form a ternary complex in vivo and enhances p14(ARF)-induced G(2) cell cycle arrest in a p53-dependent manner. We suggest that the interaction of p14(ARF) and p120(E4F) forms an important link between the p14(ARF) and p53 tumor suppressor proteins, both of which exhibit enhanced cell cycle inhibitory activity in the presence of this transcriptional repressor.
Rizos
Helen
H
Westmead Institute for Cancer Research, University of Sydney, Westmead Hospital, Westmead, New South Wales 2145, Australia. helen_rizos@wmi.usyd.edu.au
Diefenbach
Eve
E
Badhwar
Prerna
P
Woodruff
Sarah
S
Becker
Therese M
TM
Rooney
Robert J
RJ
Kefford
Richard F
RF
D017504:Adenovirus E4 Proteins / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics*; D005786:Gene Expression Regulation; D019942:Genes, p16; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics* / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics
D017504:Adenovirus E4 Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D025803:Tumor Suppressor Protein p14ARF; C411663:transcription factor p120(E4F)