Role of the N-terminal activation domain of the coiled-coil coactivator in mediating transcriptional activation by beta-catenin.
The coiled-coil coactivator (CoCoA) is involved in transcriptional activation of target genes by nuclear receptors and the xenobiotic aryl hydrocarbon receptor, as well as target genes of the Wnt signaling pathway, which is mediated by the lymphocyte enhancer factor (LEF)/T cell factor transcription factors and the coactivator beta-catenin. The recruitment of CoCoA by nuclear receptors is accomplished by the interaction of the central coiled-coiled domain of CoCoA with p160 coactivators; the C-terminal activation domain (AD) of CoCoA is used for downstream signaling, whereas the function of the N-terminal region is undefined. Here we report that the N terminus of CoCoA contains another AD, which is necessary and sufficient for synergistic activation of LEF1-mediated transcription by CoCoA and beta-catenin. The N-terminal AD contains a p300 binding motif, which is important for synergistic cooperation of CoCoA and p300 as coactivators for LEF1 and beta-catenin. p300 contributes to the function of the CoCoA N-terminal AD primarily through its histone acetyltransferase activity. Moreover, in cultured cells, endogenous p300 is recruited to the promoter of an integrated reporter gene by the N terminus of CoCoA. Thus, the coactivator function of CoCoA for nuclear receptors and LEF1/beta-catenin involves differential utilization of two different CoCoA ADs.
Yang
Catherine K
CK
Department of Biochemistry and Molecular Biology, University of Southern California, 1333 San Pablo Street, MCA 51A, Los Angeles, California 90089-9151, USA.
Kim
Jeong Hoon
JH
Stallcup
Michael R
MR
D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D051548:Histone Acetyltransferases / Q000378:metabolism; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D051176:beta Catenin / Q000378:metabolism*; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D051821:Lymphoid Enhancer-Binding Factor 1; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C495392:CALCOCO1 protein, human; C491310:GRIP1 protein, human