CBP/p300 histone acetyl-transferase activity is important for the G1/S transition.
Transforming viral proteins such as E1A which force quiescent cells into S phase have two essential cellular target proteins, Rb and CBP/p300. Rb regulates the G1/S transition by controlling the transcription factor E2F. CBP/p300 is a transcriptional co-activator with intrinsic histone acetyl-transferase activity. This activity is regulated in a cell cycle dependent manner and shows a peak at the G1/S transition, suggesting a function for CBP/p300 in this crucial step of the cell cycle. Here, we have artificially modulated CBP/p300 levels in individual cells through microinjection of specific antibodies and expression vectors. We show that CBP/p300 is required for cell proliferation and has an essential function during the G1/S transition. Using the same microinjection system and GFP-reporter vectors, we demonstrate that CBP/p300 is essential for the activity of E2F, a transcription factor that controls the G1/S transition. In addition, our results suggest that CBP HAT activity is required both for the G1/S transition and for E2F activity. Thus CBP/p300 seems to be a versatile protein involved in opposing cellular processes, which raises the question of how its multiple activities are regulated.
Ait-Si-Ali
S
S
Laboratoire 'Oncogenèse, Différenciation et Transduction du Signal' CNRS IFC-01, 7 rue Guy Moquet, 94801 Villejuif, France.
Polesskaya
A
A
Filleur
S
S
Ferreira
R
R
Duquet
A
A
Robin
P
P
Vervish
A
A
Trouche
D
D
Cabon
F
F
Harel-Bellan
A
A
D016475:3T3 Cells; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D050684:E2F Transcription Factors; D016193:G1 Phase; D051548:Histone Acetyltransferases; D051379:Mice; D016296:Mutagenesis; D011485:Protein Binding; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase; D017384:Sequence Deletion; D035181:TATA-Box Binding Protein; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D051548:Histone Acetyltransferases; D056465:Retinoblastoma-Binding Protein 1; D035181:TATA-Box Binding Protein; D050680:Transcription Factor DP1; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C533431:Arid4a protein, mouse