Prohibitin participates in the molecular mechanism of E2F cell cycle regulation pathway by interacting with Retinoblastoma protein

Human prohibitin protein was first linked to human cancers by the discoveries of prohibitin mutations in breast cancers. Subsequent studies showed that PHB is a tumor suppressor involved in the E2F cell cycle regulation pathways that can affect cell proliferation, differentiation and apoptosis. And PHB has been identified as drug target protein for cancer treatment.The methods such as SPR, ChIP will be used in this project to find out the interaction strength changes between PHB, its mutants in breast cancer patients and Rb protein both in vitro and in vivo,and we will analyze the relationships between the mutations and the PHB functions.NMR spectroscopy methods will also be used to study the dynamic characteristics of the PHB and Rb protein interactions, and we will analyze the structural basis for the interactions.On these basis,it will be revealed the molecular mechanism of the protein interaction of PHB and Rb protein involved in the E2F-mediated cell cycle regulatory pathways, the structural basis for the PHB functions will be analyzed and the clues for drug design and development will be provided.