Therapeutic Strategies To Combat Cancers Caused By HMGA1a

The protein HMGA1a adopts dynamic, more compact structures that depend on its phosphorylation. A malfunction of HMGA1a can lead to cancer. The researchers considering therefore expect their results to form a basis for future therapeutic strategies to combat cancers caused by HMGA1a. While the correct function of many proteins depends on their three-dimensional structure, some appear to adopt random forms.

For one of them, a team of researchers at Ruhr-Universitat Bochum (RUB) has shown that the supposed disorder is not disorder after all the protein HMGA1a adopts dynamic, more compact structures that depend on its phosphorylation. A malfunction of HMGA1a can lead to cancer. The researchers led by Professor Raphael Stoll therefore expect their results to form a basis for future therapeutic strategies to combat cancers caused by HMGA1a.

Therapeutic strategies for cancer

Many but not all proteins in a living cell have a defined three-dimensional structure, which is absolutely necessary for their correct activity. The interrelationship between the structure and function of proteins is the focus of many research initiatives that extend to the development of innovative drugs. Despite or precisely because of this remarkable feature; these proteins have special, sometimes crucial, functions in both healthy and disease causing processes.

These include, for example, the regulation of the cell cycle, the transmission of biological signals, and the development of cancer or neurodegenerative diseases; such as Alzheimer’s or Parkinson’s disease. One of these seemingly disordered proteins is the high-mobility group protein A1a. It is highly abundant in the cell nucleus and is important for embryonic development; cell differentiation, and is also involved in the development of uncontrolled cell proliferations, called neoplasia.

The HMGA1a protein

This has an effect on the electrostatic network in the HMGA1a protein; and thus changes the dynamic structural ensemble of this protein. Further experiments revealed that these changes even affect the ability of the HMGA1a protein; to bind to its natural target sequence in the DNA of the cell nucleus. The Bochum-based research team has succeeded; in showing for the first time that the HMGA1a protein does not adopt completely random forms; but rather dynamic, more compact structures.

This enabled the researchers to create the first full-length structural model of the HMGA1a protein. This has an effect on the electrostatic network in the HMGA1a protein; and thus changes the dynamic structural ensemble of this protein. Further experiments revealed that these changes even affect the ability of the HMGA1a protein; to bind to its natural target sequence in the DNA of the cell nucleus.