Identification of the Interaction Domains in the ENO1/Hsp70 Complex, Delve into Novel Potential Therapeutic Target

Abstract

Abstract Alpha-enolase is a multifunctional protein with oncogenic roles. First described as a glycolytic enzyme the protein performs different functions according to its cellular localization, post-translational modifications, and binding partners. Cell surface-localized alpha-enolase serves as a plasminogen binding receptor and it has been detected in several cell types, including various tumor cells. Plasminogen system plays a crucial role in pathological events such as tumor cell invasion and metastasis. We have previously demonstrated that the interaction of alpha-enolase with the multifunctional chaperone Hsp70 increases its surface localization and the migratory and invasive capacity of breast cancer cells, thus representing a novel potential target to counteract the metastatic potential of tumors. Here we used experimental and computational approaches for the mapping and hot-spot prediction of the interaction domains between alpha-enolase and Hsp70. The molecular definition of this disease-relevant protein-protein interaction will provide the basis for the design of specific inhibitors as potential anti-metastatic agents.