Transcriptional co-repressors of Runx2

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Runx2 is an essential transcription factor for skeletal mineralization because it stimulates osteoblast differentiation of mesenchymal stem cells, promotes chondrocyte hypertrophy, and contributes to endothelial cell migration and vascular invasion of developing bones. Runx2 is also expressed during mouse embryo development in nascent mammary gland epithelium. Recent evidence implicates deregulation of Runx2 as a contributing factor in breast cancer-induced osteolysis and invasion, as well as in ectopic vascular calcification. Like other Runt domain proteins, Runx2 is a context-dependent transcriptional activator and repressor of genes that regulate cellular proliferation and differentiation. Proteins that temporally and spatially associate with Runx2 dictate these opposing transcriptional activities. Recent studies have identified several co-repressor proteins that bind to Runx2 to regulate gene expression. These co-factors include histone deacetylases (HDACs), transducin-like enhancer of split (TLE) proteins, mSin3a, and yes-associated protein (YAP). These proteins do not bind DNA themselves and appear to act by preventing Runx2 from binding DNA, altering chromatin structure, and/or by possibly blocking co-activator complexes. The nuclear localization of several of these factors is regulated by extracellular signaling events. Understanding the mechanisms whereby co-repressor proteins affect Runx2 activity during normal cellular development and tumor progression will identify new therapeutic targets for skeletal disorders such as osteoporosis and for bone metastatic cancers.

Original languageEnglish (US)
Pages (from-to)54-64
Number of pages11
JournalJournal of Cellular Biochemistry
Volume98
Issue number1
DOIs
StatePublished - May 1 2006
Externally publishedYes

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Co-Repressor Proteins
Core Binding Factor Alpha 1 Subunit
Bone
Proteins
Transducin
Vascular Calcification
Bone Neoplasms
Osteolysis
Histone Deacetylases
Deregulation
DNA
Osteoblasts
Endothelial cells
Human Mammary Glands
Chondrocytes
Stem cells
Mesenchymal Stromal Cells
Gene expression
Hypertrophy
Osteoporosis

Keywords

  • Bone
  • HDAC
  • Metastasis
  • mSin3A
  • TLE
  • YAP

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Transcriptional co-repressors of Runx2. / Westendorf, Jennifer J.

In: Journal of Cellular Biochemistry, Vol. 98, No. 1, 01.05.2006, p. 54-64.

Research output: Contribution to journalArticle

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