Interactome of Ixr1, HMGB1 and HMGB2 proteins in relation to their cellular functions

Abstract

The Saccharomyces cerevisiae protein, Ixr1, and human HMGB1 and HMGB2 proteins belong to the HMGB protein family. The main objective of this work was to identify new proteins binding Ixr1, HMGB1 and HMGB2 in order to increase the knowledge about their cellular functions. In yeast Ixr1 has activator or repressor activity on transcription in different promoters and controls the hypoxic response. The transcriptional activator domain of Ixr1 has been identified in its NH2 term in this study. Interactome studies show that Ixr1 binds to Ssn8 and this interaction might mediate the repressor function of Ixr1 on several promoters. Other proteins identified share functions associated to glucose metabolism, stress, and ribosome biogenesis among others. Differential phosphorylation of Ixr1 was observed depending on oxygen availability. The HMGB1 and HMGB2 interactomes were studied using different techniques as yeast two‐hybrid assays and purification methods coupled with mass spectrometry. This study was carried out in cancerous and noncancerous ovarian and prostate epithelial cells. Results showed the wide range of functions linked to their interacting partners. The interaction of HMGB1 with KRT7 and RBBP7 was validated by complementary techniques. HMGB1 specific interactions associated to cisplatin treatment of these cells were also identified in this study.