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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. However, 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 this study, we systematically studied HIF1A cofactors in eight cancer cell lines using the computational motif mining tool, SIOMICS, and discovered 201 potential HIF1A cofactors, which included 21 of the 29 known HIF1A cofactors in public databases. These 201 cofactors were statistically and biologically significant, with 19 of the top 37 cofactors in our study directly validated in the literature. The remaining 18 were novel cofactors. These discovered cofactors can be essential to HIF1A’s regulatory functions and may lead to the discovery of new therapeutic targets in cancer treatment.

 

Recent geochemical evidence confirms the oxidized nature of arc magmas, but the underlying processes that regulate the redox state of the subarc mantle remain yet to be determined. We established a link between deep subduction-related fluids derived from dehydration of serpentinite ± altered oceanic crust (AOC) using B isotopes and B/Nb as fluid proxies, and the oxidized nature of arc magmas as indicated by Cu enrichment during magma evolution and V/Yb. Our results suggest that arc magmas derived from source regions influenced by a greater serpentinite (±AOC) fluid component record higher oxygen fugacity. The incorporation of this component into the subarc mantle is controlled by the subduction system’s thermodynamic conditions and geometry. Our results suggest that the redox state of the subarc mantle is not homogeneous globally: Primitive arc magmas associated with flat, warm subduction are less oxidized overall than those generated in steep, cold subduction zones.