High mobility group AT-hook protein 2 (HMGA2) (HMGA2)

High mobility group AT-hook protein 2 (HMGA2), historically known as HMGI-C, is a non-histone architectural transcription factor that is essential for embryonic development. It functions by binding to the minor groove of AT-rich DNA sequences through three AT-hook motifs, which induces conformational changes in the DNA to facilitate the assembly of transcriptional complexes called enhanceosomes. While its expression is high during fetal growth, it is largely silenced in adult tissues, with the exception of certain stem cell populations. In many human malignancies, HMGA2 is aberrantly re-expressed or rearranged, where it acts as an oncogene by promoting the epithelial-to-mesenchymal transition (EMT), cell proliferation, and resistance to apoptosis. Beyond cancer, HMGA2 is involved in the development of benign mesenchymal tumors such as lipomas and leiomyomas, and it plays a role in adipogenesis and diet-induced obesity. The protein is considered a promising therapeutic target, with research focusing on minor groove binders like netropsin and small molecules like suramin to inhibit its DNA-binding activity. Additionally, HMGA2 serves as a valuable prognostic biomarker in various cancers and a predictive marker for response to TGF-beta targeted therapies.

Other names

High mobility group protein HMGI-CHMGICBABLLIPOSRS5STQTL9

Competitive inhibition of DNA binding at AT-rich minor groove sites; inhibition of transcriptional regulatory activity and downstream oncogenic signaling.