High mobility group AT-hook 2 protein (HMGA2)

High mobility group AT-hook 2 protein (HMGA2) is a small, non-histone chromatin architectural protein characterized by three positively charged AT-hook DNA-binding domains and a negatively charged C-terminal region. It modulates chromatin structure and regulates gene transcription through structural alterations of DNA, facilitating or restricting access to various transcription factors and chromatin-associated complexes. HMGA2 plays central roles in cellular proliferation, differentiation, cell cycle progression, apoptosis, DNA repair (exhibiting both promotion and impairment functions), epithelial-mesenchymal transition (EMT), and maintenance of telomere stability. In adult tissues, HMGA2 is typically minimally expressed but is aberrantly upregulated in numerous cancers, contributing to tumorigenesis, metastasis, and chemoresistance. It is regulated by microRNA let-7, and alterations in its expression or genetic structure are associated with disease states such as obesity, lipomas, and malignancies. HMGA2 is considered a valid therapeutic target for cancer and potentially anti-obesity therapies, with experimental compounds such as suramin and synthetic peptides shown to inhibit its function by blocking DNA binding.

Other names

HMGA2High mobility group protein A2High mobility group protein isoform CHMGI-C

Competitive inhibition of DNA binding (e.g., suramin binding to the AT-hook domains prevents interaction with DNA); Inhibition of chromatin remodeling (C-terminal peptides block AT-hook-mediated DNA association)