Co-activator activator (CoAA) prevents the transcriptional activity of runt domain transcription factors

Xiaodong Li, Luke H. Hoeppner, Eric D. Jensen, Rajaram Gopalakrishnan, Jennifer J. Westendorf

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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 deacetylaseindependent 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.

Original languageEnglish (US)
Pages (from-to)378-387
Number of pages10
JournalJournal of Cellular Biochemistry
Volume108
Issue number2
DOIs
StatePublished - Oct 1 2009

Keywords

  • AML3
  • Axin2
  • Cbfa1
  • CoAM
  • Osteosarcoma
  • RBM14
  • Runx1
  • Runx3

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