Page 150 - ebook

[B. Cell Biology/Stem Cell] B-10

Fe65 promotes the degradation of Jagged1 by forming a

trimeric complex with Jagged1 and the E3 ligase Neurl1

Eun-Hye Jo¹, Mi-Yeon Kim¹, So-I Noh¹, Hyung-Ju Lee¹, Hee-Sae Park¹*

¹School of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, Korea

Fe65 is a highly conserved adaptor protein that interacts with several binding partners. Fe65 binds proteins to
mediate various cellular processes. But the interacting partner and the regulatory mechanisms controlled by Fe65

are largely unknown. In this study, we found that Fe65 interacts with the C-terminus of Jagged1. Furthermore, Fe65
negatively regulates AP1-mediated Jagged1 intercellular domain transactivation in a Tip60- independent manner.

We found that Fe65 triggers the degradation of Jagged1, but not the Jagged1 intracellular domain (JICD), through
both proteasome and lysosome pathways. We also showed that Fe65 promotes recruitment of the E3 ligase

Neuralized-like 1 (Neurl1) tomembrane-tethered Jagged1 and monoubiquitination of Jagged1. These three proteins
form a stable trimeric complex, thereby decreasing Jagged1 targeting by ubiquitinmediated degradation.

Consequently, Jagged1 is a novel binding partner of Fe65, and Fe65 may act as a novel effector of Jagged1 signaling.