Pellino1 specifically binds to phospho-Thr18 of p53 and is recruited to sites of DNA damage

• Main Authors: Dai, Liang, Lin, Jianqing, Aminahtusaidah Said, Yau, Yin Hoe, Shochat, Susana Geifman, Ruiz-Carrillo, David, Sun, Kang, Chandrasekaran, Ramya, Sze, Siu Kwan, Lescar, Julien, Cheung, Peter Ching For
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2021
• Subjects: Science::Biological sciences; Pellino1; p53
• Online Access: https://hdl.handle.net/10356/151627
• Institution: Nanyang Technological University

Pellino1 is an E3 ubiquitin ligase that plays a key role in positive regulation of innate immunity signaling, specifically required for the production of interferon when induced by viral double-stranded RNA. We report the identification of the tumor suppressor protein, p53, as a binding partner of Pellino1. Their interaction has a K of 42 ± 2 μM and requires phosphorylation of Thr18 within p53 and association with the forkhead-associated (FHA) domain of Pellino1. We employed laser micro-irradiation and live cell microscopy to show that Pellino1 is recruited to newly occurring DNA damage sites, via its FHA domain. Mutation of a hitherto unidentified nuclear localization signal within the N-terminus of Pellino1 led to its exclusion from the nucleus. This study provides evidence that Pellino1 translocates to damaged DNA in the nucleus and has a functional role in p53 signaling and the DNA damage response.