E2F1 binds to the peptide-binding groove within the BIR3 domain of cIAP1 and requires cIAP1 for chromatin binding

• DOI: 10.1371/journal.pone.0206253
• Publication Date: 2018-10-25T21:17:41Z
• Authors: Jennifer Allègre; Jessy Cartier; Valérie Glorian; Nathalie Droin; Baptiste Dumetier; Cémile Kayaci; Jean Berthelet; Simon Gemble; Céline Vuillier; Laurent Maillet; Carmen Garrido; Laurence Dubrez
• Keywords: E2F1

The cellular inhibitor of apoptosis 1 (cIAP1) is an E3-ubiquitin ligase that regulates cell signaling pathways involved in fundamental processes including death, proliferation, differentiation and inflammation. It recruits ubiquitination substrates thanks to the presence three baculoviral IAP repeat (BIR) domains at its N-terminal extremity. We previously demonstrated cIAP1 promoted E2 factor (E2F1) transcription factor. Moreover, we showed was required for E2F1 stabilization during S phase cycle response DNA damage. Here, report binds within BIR3 domain. contains a surface hydrophobic groove specifically anchors conserved binding motif (IBM) found number intracellular proteins Smac. Smac N-7 peptide includes IBM, as well mimetic, competed with interaction demonstrating importance BIR groove. first alpha-helix binding, mimetics. Overexpression modified profile E2F1, increasing ratio conjugated K11- K63-linked ubiquitin chains, decreasing proportion by K48-linked chains. ChIP-seq analysis recruitment onto chromatin. Lastly, identified E2F-binding site on cIAP1-encoding birc2 gene promoter, suggesting retro-control regulation loop.