High mobility group I/Y: multifunctional chromosomal proteins causally involved in tumor progression and malignant...

The family of chromosomal high mobility group I/Y consists of proteins involved in gene regulation and chromatin organization. A common feature of these proteins is the presence of multiple copies of DNA binding domains (DBD), the so-called AT-hooks. Bi- or tridendate interaction of two or three DBDs with appropriately spaced AT-rich DNA tracts forms the basis of binding specificity of the HMGI/Y proteins. Binding of HMGI/Y to structure-specific targets within the minor groove affects the DNA conformation and facilitates binding of transcription factors. Phosphorylation by casein kinase 2, Cdc2, and other kinases attenuates the DNA-binding affinity of HMGI/Y and the extent of perturbation in DNA structure induced by HMGI/Y-binding. In the human genome, two genes coding for HMGI/Y proteins, HMGI(Y) and HMGI-C, have been found. Both are abundantly transcribed in early embryonic and undifferentiated cells. An over-expression of the HMGI/Y proteins is characteristic for malignant tumors, suggesting a relation between high titers of the proteins and neoplastic phenotype. Defects in the HMGI-C gene have been found in a variety of benign tumors, such as uterine leiomyomas, endometrial polyps, lipomas, and pulmonary chondroid hamartomas.