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(Journal Article) |
Biochemical and biophysical research communications 513 (3): 714-720 (2019)
Pellino1 specifically binds to phospho-Thr18 of p53 and is recruited to sites of DNA damage.
Liang Dai
,
Jianqing Lin
,
Aminahtusaidah Binte Said
,
Yin Hoe Yau
,
Susana Geifman Shochat
,
David Ruiz-Carrillo
,
Kang Sun
,
Ramya Chandrasekaran
,
Siu Kwan Sze
,
Julien Lescar
,
Peter Cf Cheung
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.