PMID- 11443112 OWN - NLM STAT- MEDLINE DCOM- 20011011 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 276 IP - 36 DP - 2001 Sep 7 TI - Identification and characterization of RRM-containing coactivator activator (CoAA) as TRBP-interacting protein, and its splice variant as a coactivator modulator (CoAM). PG - 33375-83 AB - We previously cloned and characterized thyroid hormone receptor-binding protein (TRBP) as an LXXLL-containing general coactivator that associates with coactivator complexes through its C terminus. To identify protein cofactors for TRBP action, a Sos-Ras yeast two-hybrid cDNA library was screened using TRBP C terminus as bait. A novel coactivator was isolated, coactivator activator (CoAA), that specifically associates with TRBP. Human CoAA is composed of 669 amino acids with a TRBP-interacting domain and two highly conserved RNA recognition motifs (RRM) commonly found in ribonucleoproteins. A splice variant lacking the entire TRBP-interacting domain was also isolated as a coactivator modulator (CoAM), a 156-amino acid protein containing only the RRM region. Human CoAA and CoAM mRNAs are encoded by a single gene located on chromosome 11q13; alternative splicing in exon 2 of CoAA yields CoAM. CoAA interacts with both TRBP and p300 in vitro. In addition, CoAA potently coactivates transcription mediated by multiple hormone-response elements and acts synergistically with TRBP and CREB-binding protein (CBP). Furthermore, CoAA is associated with the DNA-dependent protein kinase-poly(ADP-ribose) polymerase complex. Strikingly, CoAM, which lacks a TRBP-interacting domain, strongly represses both TRBP and CBP action suggesting that CoAM may modulate endogenous CoAA function. These data suggest that CoAA may serve as a mediator of coactivators such as TRBP in gene activation. FAU - Iwasaki, T AU - Iwasaki T AD - Lilly Research Laboratories, Department of Gene Regulation, Bone and Inflammation Research, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. FAU - Chin, W W AU - Chin WW FAU - Ko, L AU - Ko L LA - eng SI - GENBANK/AF315632 SI - GENBANK/AF315633 SI - GENBANK/AF327567 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20010706 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Amino Acids) RN - 0 (Carrier Proteins) RN - 0 (DNA, Complementary) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Nuclear Proteins) RN - 0 (RBM14 protein, human) RN - 0 (RNA, Messenger) RN - 0 (RNA-Binding Proteins) RN - 0 (Rbm14 protein, rat) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Recombinant Proteins) RN - 0 (Trans-Activators) RN - 136628-24-5 (trans-activation responsive RNA-binding protein) RN - EC 2.3.1.48 (E1A-Associated p300 Protein) RN - EC 2.3.1.48 (Ep300 protein, mouse) RN - EC 2.3.1.48 (Ep300 protein, rat) RN - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) RN - EC 2.5.1.18 (Glutathione Transferase) SB - IM MH - *Alternative Splicing MH - Amino Acid Sequence MH - Amino Acids/chemistry MH - Animals MH - Base Sequence MH - Carrier Proteins/*chemistry/*genetics MH - Cell Nucleus/metabolism MH - Cells, Cultured MH - Chromosomes, Human, Pair 11 MH - Cloning, Molecular MH - DNA, Complementary/metabolism MH - E1A-Associated p300 Protein MH - Enzyme Activation MH - Exons MH - Gene Library MH - Glutathione Transferase/metabolism MH - Humans MH - *Intracellular Signaling Peptides and Proteins MH - Introns MH - Mice MH - Models, Genetic MH - Molecular Sequence Data MH - Nuclear Proteins/metabolism MH - Plasmids/metabolism MH - Poly(ADP-ribose) Polymerases/metabolism MH - Protein Binding MH - Protein Structure, Tertiary MH - RNA, Messenger/metabolism MH - RNA-Binding Proteins/metabolism MH - Rats MH - Recombinant Fusion Proteins/metabolism MH - Recombinant Proteins/metabolism MH - Sequence Homology, Amino Acid MH - Temperature MH - Tissue Distribution MH - Trans-Activators/metabolism MH - Transcription, Genetic MH - Transfection MH - Two-Hybrid System Techniques EDAT- 2001/07/10 10:00 MHDA- 2001/10/12 10:01 CRDT- 2001/07/10 10:00 PHST- 2001/07/10 10:00 [pubmed] PHST- 2001/10/12 10:01 [medline] PHST- 2001/07/10 10:00 [entrez] AID - S0021-9258(19)34724-6 [pii] AID - 10.1074/jbc.M101517200 [doi] PST - ppublish SO - J Biol Chem. 2001 Sep 7;276(36):33375-83. doi: 10.1074/jbc.M101517200. Epub 2001 Jul 6.