BoneKEy Reports | BoneKEy Watch
Mastermind-like protein 1 interacts with Runx2 in bone development
DOI:10.1038/bonekey.2013.81
Runt-related transcription factor 2 (Runx2) is recognized as a master regulator in bone development. Watanabe et al. performed a systematic screen of around 10 000 cDNA clones in an effort to identify factors that interact with and activate Runx2, thus impacting on the differentiation of key osteoblastic precursors during embryogenesis.
One factor with particularly strong activity was a clone that represented Mastermind-like protein 1(MAML1). This protein, which consists of 1016 amino acids, was found to enhance the activity of Runx2, but in a manner that was independent of Notch signaling. This resulted in Runx2-mediated osteoblastic differentiation.
MAML1 knockout mice were analyzed and found to have obvious skeletal abnormalities. Their growth was stunted in comparison to wild-type mice and they had a shorter mineralized region in their long bones. In the femoral diaphysis, MAML1−/− mice had a significantly reduced area of primary spongiosa, which suggested that their chondrocytes had not matured normally. The authors conclude that interaction between MAML1 and Runx2 is crucial for normal bone development
Editor’s comment: The full details of the molecular interaction between MAML1 and Runx2 are yet to be clarified. It will be interesting to find out whether MAML1 expression is modified by factors or conditions that affect osteoblast/chondrocyte differentiation.
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