HCF-1 complexes: how are they formed? What is their role?

Host-Cell Factor 1 (HCF-1) is a ubiquitously expressed cellular protein discovered because it associates with the viral protein VP16 and the cellular protein Oct-1 to create the VP16-induced complex (VIC) that regulates the viral immediate-early gene expression during the lytic phase of the Herpes Simplex Virus (HSV).

But HCF-1 can interact also with cellular transcriptional factors and chromatin modifiers to regulate cellular gene expression as well. In fact, HCF-1 is involved in growth, death, differentiation, proliferation, response to stress, liver regeneration, tumorigenesis, stem pluripotency, embryonic differentiation and development.

My research proposal is focused on the N-terminus of HCF-1, on both the Kelch-like and the basic domains. This part of the protein is a protein-protein interaction module whose mutations have been found in patients affected by non-syndromic intellectual disability and cobalamin disorder.

With my thesis I will try, first of all, to understand the effects of those mutations at a molecular level with a particular attention to the protein-protein interactions. Then I will try to figure out how different proteins with HCF-1 Binding Motif (HBM) could interact at the same time with HCF-1.