Ca2+/Calmodulin-dependent regulation of the MiT-TFE family

The precise control and regulation of gene activity is essential for a functioning organism. This control takes place individually in each cell and differs greatly depending on whether it is a muscle cell, nerve cell or immune cell. Therefore, there are so-called transcription factors that have the task of regulating the gene activity of a cell precisely. The importance of this regulation becomes clear when one considers the consequences of a dysfunction. Calcium is an important element in the control of a cell, as it serves as a second messenger substance. In this project the calcium-dependent regulation of the MiT-TFE protein family is investigated. The MiT-TFE protein family is one of those transcription factors and acts as a guardian of gene activity. Here it primarily regulates autophagy, an important cellular recycling mechanism. If this protein family is activated in an uncontrolled manner, it can lead to cancer (especially skin cancer). It is therefore of the utmost importance for me to find out how exactly this calcium-dependent control takes place and why or where there are sometimes weaknesses in the control mechanism. Together with a structural biology team (EMBL Hamburg) I would like to find out how this protein family works in order to be able to pharmacologically counteract an incorrect activation and the associated far-reaching consequences. So far we have already been able to bring an important protein into connection with the MiT-TFE activity, calmodulin. Calmodulin is an extremely important calcium-dependent protein and acts here as a linker between calcium and MiT-TFE activation. We are the first research team to establish a connection between calmodulin and MiT-TFE activity. With this pioneering work, we can show a new step in transcription factor activation and hopefully lay another cornerstone for successful skin cancer therapy.