Distinct roles of the co-activators p300 and CBP in retinoic-acid-induced F9-cell differentiation

Abstract

The related proteins p300 and CBP (cAMP-response-element-binding protein (CREB)-binding protein)) are transcriptional co-activators that act with other factors to regulate gene expression and play roles in many cell-differentiation and signal transduction pathways. Both proteins have intrinsic histone-acetyltransferase activity and may act directly on chromatin, of which histone is a component, to facilitate transcription. They are also involved in growth control pathways, as shown by their interaction with the tumour suppressor p53 and the viral oncogenes E1A and SV40 T antigen. 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 carcinoma F9 cells, using hammerhead ribozymes capable of cleaving either p300 or CBP messenger RNAs. F9 cells expressing a p300-specific ribozyme became resistant to retinoic-acid-induced differentiation, whereas cells expressing a CBP-specific ribozyme were unaffected. Similarly, retinoic-acid-induced transcriptional upregulation of the cell-cycle inhibitor p21Cip1 required normal levels of p300, but not CBP, whereas the reverse was true for p27Kip1. In contrast, both ribozymes blocked retinoic-acid-induced apoptosis, indicating that both co-activators are required for this process. Thus, despite their similarities, p300 and CBP have distinct functions during retinoic-acid-induced differentiation of F9 cells.

Lithium inhibits Smad3/4 transactivation via increased CREB activity induced by enhanced PKA and AKT signaling

“…This observation is supported by a report that retinoic acid-induced cell differentiation and transcriptional upregulation of p21 Cip1 requires normal levels of p300, but not CBP, in F9 cells (Kawasaki et al, 1998). CBP and p300 share a high degree of structural homology and both bind the transcription factor CREB (Chan and La Thangue, 2001;Vo and Goodman, 2001).…”

Impaired expression of a human septin family gene Bradeion inhibits the growth and tumorigenesis of colorectal cancer in vitro and in vivo

“…The ribozyme transcripts by this pol III -dependent expression system are much higher than that of pol II expression system. 10,11 The target sequences of these ribozymes and maxizymes in Bradeion mRNA are shown in Figure 1, A and B, and selected cleavage sites are indicated by black boxes.…”

“…Stably transfected SW480 cells that harbored a ribozyme and /or maxizyme were selected by G418 (ribozyme and maxizyme ) and hygromycin (maxizyme ). 10,11 A total of 66 independent lines for each mutant ( Bradeion single mutant, Bradeion single mutant, and…”

Significant activity of a modified ribozyme with N7‐deazaguanine at G10.1: the double‐metal‐ion mechanism of catalysis in reactions catalysed by hammerhead ribozymes

“…1A, were synthesized chemically on a DNA/RNA synthesizer [model 394; PE Applied Biosystems (ABI), division of Perkin Elmer, Foster City, CA]. R34 is designed to cleave p300 mRNA (Kawasaki et al 1998). Reagents for RNA synthesis were purchased from Glen Research (Sterling, VA).…”