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

Biochem Biophys Res Commun. 2019 Jun 4;513(3):714-720. doi: 10.1016/j.bbrc.2019.03.095. Epub 2019 Apr 12.

Abstract

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 Kd 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.

Keywords: DNA damage response; FHA domain; Pellino1; Threonine phosphorylation; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA Damage*
  • HEK293 Cells
  • Humans
  • Models, Molecular
  • Nuclear Proteins / analysis
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / metabolism*
  • Ubiquitin-Protein Ligases / analysis
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Nuclear Proteins
  • Tumor Suppressor Protein p53
  • PELI1 protein, human
  • Ubiquitin-Protein Ligases