TEThered to Runx: novel binding partners for runx factors.
RUNX transcription factors reside in the nuclear matrix where they integrate numerous signaling pathways to regulate gene expression and affect tissue development, regeneration, and tumorigenesis. An affinity purification and proteomic experiment was performed to identify novel Runx2 binding partners. The interactions between Runx2 and two nuclear factors (Ddx5 and CoAA) identified in this screen were previously described. Coactivator activator (CoAA) bound the DNA binding domain of Runx2 and prevented Runx-driven gene expression. The YxxQ motif in CoAA was required for Runx2 interactions. Members of the FET/TET family of proteins, including FUS/TLS and EWSR1, contain a similar motif and were hypothesized to interact with Runx2. Here, we provide evidence that FUS/TLS, EWSR1, and the Ewing's sarcoma t(12;21) fusion protein EWS-FLI bind Runx2 and alter its transcriptional activity. Potential roles of protein complexes containing FET/TET and RUNX family members during tumor formation and mesenchymal progenitor cell differentiation are discussed.
Li
Xiaodong
X
Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Decker
Matthew
M
Westendorf
Jennifer J
JJ
D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D050657:Core Binding Factor alpha Subunits / Q000378:metabolism*; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D011485:Protein Binding; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D002148:Calmodulin-Binding Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D050676:Core Binding Factor Alpha 2 Subunit; D050657:Core Binding Factor alpha Subunits; C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; D014157:Transcription Factors