A systematic study of HIF1A cofactors in hypoxic cancer cells

Abstract

Hypoxia inducible factor 1 alpha (HIF1A) is a transcription factor (TF) that forms highly structural and functional protein-protein interactions with other TFs to promote gene expression in hypoxic cancer cells. Despite the importance of these TF-TF interactions, we still lack a comprehensive view of many of the TF cofactors involved and how they cooperate in hypoxic cancer cells. In this study, we systematically studied HIF1A cofactors in eight cancer cell lines and discovered 201 potential HIF1A cofactors. These cofactors were statistically and biologically significant, with 30 of the top 37 cofactors validated or supported in the literature. Moreover, these predicted cofactors include 21 of the 29 known HIF1A TF cofactors in public databases. These discovered cofactors can be essential to HIF1As regulatory functions and may lead to the discovery of new therapeutic targets in cancer treatment.