Differential use of functional domains by coiled-coil coactivator in its synergistic coactivator function with beta-catenin or GRIP1.
beta-Catenin, a pivotal component of the Wnt-signaling pathway, binds to and serves as a transcriptional coactivator for the T-cell factor/lymphoid enhancer factor (TCF/LEF) family of transcriptional activator proteins and for the androgen receptor (AR), a nuclear receptor. Three components of the p160 nuclear receptor coactivator complex, including CARM1, p300/CBP, and GRIP1 (one of the p160 coactivators), bind to and cooperate with beta-catenin to enhance transcriptional activation by TCF/LEF and AR. Here we report that another component of the p160 nuclear receptor coactivator complex, the coiled-coil coactivator (CoCoA), directly binds to and cooperates synergistically with beta-catenin as a coactivator for AR and TCF/LEF. CoCoA uses different domains to bind GRIP1 and beta-catenin, and it uses different domains to transmit the activating signal to the transcription machinery, depending on whether it is bound to GRIP1 or beta-catenin. CoCoA associated specifically with the promoters of transiently transfected and endogenous target genes of TCF/LEF, and reduction of the endogenous CoCoA level decreased the ability of TCF/LEF and beta-catenin to activate transcription of transient and endogenous target genes. Thus, CoCoA uses different combinations of functional domains to serve as a physiologically relevant component of the Wnt/beta-catenin signaling pathway and the androgen signaling pathway.
Yang
Catherine K
CK
Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, California 90089, USA.
Kim
Jeong Hoon
JH
Li
Hongwei
H
Stallcup
Michael R
MR
D000818:Animals; D019556:COS Cells; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002645:Chickens; D002522:Chlorocebus aethiops; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D051176:beta Catenin / Q000378:metabolism / Q000502:physiology*
C495392:CALCOCO1 protein, human; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C491310:GRIP1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D009419:Nerve Tissue Proteins; D051820:TCF Transcription Factors; D014157:Transcription Factors; D051176:beta Catenin; D005982:Glutathione Transferase