Distinct roles of the co-activators p300 and CBP in retinoic-acid-induced F9-cell differentiation.
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.
Kawasaki
H
H
Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Tsukuba Science City, Japan.
Eckner
R
R
Yao
T P
TP
Taira
K
K
Chiu
R
R
Livingston
D M
DM
Yokoyama
K K
KK
D017209:Apoptosis; D050882:CREB-Binding Protein; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D016337:RNA, Catalytic / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D016337:RNA, Catalytic; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D014212:Tretinoin; D050882:CREB-Binding Protein; D018844:Cyclin-Dependent Kinases