Page 162 - ebook

[B. Cell Biology/Stem Cell] B-16

Autophagy controls tumor cell proliferation by promoting

Notch1-IC degradation

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

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

Autophagy is a highly conserved mechanism that degrades long-lived proteins and dysfunctional organelles, and
contributes to cell fate. In this study, autophagy attenuates Notch1 signaling by degrading the Notch1 intracellular

domain (Notch1-IC). Nutrient-deprivation promotes Notch1-IC phosphorylation by MEKK1 and phosphorylated
Notch1-IC is recognized by Fbw7 E3 ligase. The ubiquitination of Notch1-IC by Fbw7 is essential for the interaction

between Notch1-IC and p62 and for the formation of aggregates. Inhibition of Notch1 signaling prevents the
transformation of breast cancer cells, tumor progression, and metastasis. The expression of Notch1 and p62 is

inversely correlated with Beclin1 expression in human breast cancer patients. These results show that autophagy
inhibits Notch1 signaling by promoting Notch1-IC degradation and therefore plays a role in tumor suppression.