H. Kawasaki et al., DISTINCT ROLES OF THE COACTIVATORS P300 AND CBP IN RETINOIC-ACID-INDUCED F9-CELL DIFFERENTIATION, Nature, 393(6682), 1998, pp. 284-289
The related proteins p300 and CBP (cAMP-response-element-binding prote
in (CREB)-binding protein)) are transcriptional co-activators that act
with other factors to regulate gene expression(1-5) and play roles in
many cell-differentiation add signal transduction pathways(6-10). Bot
h proteins have intrinsic histone-acetyltransferase activity(11,12) an
d may act directly on chromatin, of which histone is a component, to f
acilitate transcription. They are also involved in growth control path
ways, as shown by their interaction with the tumour-suppressor p53 (re
fs 13-15) and the viral oncogenes E1A (refs 1, 2, 16) and SV40 T antig
en(5). Here we report functional differences of p300 and CBP in vivo.
We examined their roles during retinoic-acid-induced differentiation,
cell-cycle exit and programmed cell death (apoptosis) of embryonal car
cinoma F9 cells(17,20), using hammerhead ribozymes capable of cleaving
either p300 or CBP messenger RNAs. F9 cells expressing a p300-specifi
c ribozyme became resistant to retinoic-acid-induced differentiation,
whereas cells expressing a CBP-specific ribozyme were unaffected. Simi
larly, retinoic-acid-induced transcriptional upregulation of the cell-
cycle inhibitor p21(Cip1) required normal levels of p300, but not CBP,
whereas the reverse was true for p27(Kip1). In contrast, both ribozym
es blocked retinoic-acid-induced apoptosis, indicating that both co-ac
tivators are required for this process. Thus, despite their similariti
es, p300 and CBP have distinct functions during retinoic-acid-induced
differentiation of F9 cells.