Co-activator activator (CoAA) prevents the transcriptional activity of Runt domain transcription factors.
Runx proteins are essential for a number of developmental processes and are aberrantly expressed in many human cancers. Runx factors bind DNA and co-factors to activate or repress genes crucial for bone formation, hematopoiesis, and neuronal development. Co-activator activator (CoAA) is a nuclear protein that regulates gene expression, RNA splicing and is overexpressed in many human tumors. In this study, we identified CoAA as a Runx2 binding protein. CoAA repressed Runx factor-dependent activation of reporter genes in a histone deacetylase-independent manner. CoAA also blocked Runx2-mediated repression of the Axin2 promoter, a novel Runx target gene. The carboxy-terminus of CoAA is essential for binding the Runt domains of Runx1 and Runx2. In electophoretic mobility shift assays, CoAA inhibited Runx2 interactions with DNA. These data indicate that CoAA is an inhibitor of Runx factors and can negate Runx factor regulation of gene expression. CoAA is expressed at high levels in human fetal osteoblasts and osteosarcoma cell lines. Suppression of CoAA expression by RNA interference reduced osteosarcoma cell viability in vitro, suggesting that it contributes to the proliferation and/or survival of osteoblast lineage cells.
Li
Xiaodong
X
Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota 55905, USA.
Hoeppner
Luke H
LH
Jensen
Eric D
ED
Gopalakrishnan
Rajaram
R
Westendorf
Jennifer J
JJ
D000818:Animals; D060466:Axin Protein; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050676:Core Binding Factor Alpha 2 Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050677:Core Binding Factor Alpha 3 Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D032446:Myoblasts / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D034741:RNA, Small Interfering; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D012886:Skull / Q000166:cytology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D060466:Axin Protein; C111729:Axin2 protein, mouse; C519386:Rbm14 protein, mouse; D050659:Core Binding Factor Alpha 1 Subunit; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C436317:RBM14 protein, human; D034741:RNA, Small Interfering; C486667:Rbm14 protein, rat; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors