FBXO24 Suppresses Breast Cancer Tumorigenesis by Targeting LSD1 for Ubiquitination

Bo Dong, Xiang Song, Xinzhao Wang, Tao Dai, Jianlin Wang, Zhiyong Yu, Jiong Deng, B. Mark Evers, Yadi Wu

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Lysine-specific demethylase 1 (LSD1), a critical chromatin modulator, functions as an oncogene by demethylation of H3K4me1/2. The stability of LSD1 is governed by a complex and intricate process involving ubiquitination and deubiquitination. Several deubiquitinases preserve LSD1 protein levels. However, the precise mechanism underlying the degradation of LSD1, which could mitigate its oncogenic function, remains unknown. To gain a better understanding of LSD1 degradation, we conducted an unbiased siRNA screening targeting all the human SCF family E3 ligases. Our screening identified FBXO24 as a genuine E3 ligase that ubiquitinates and degrades LSD1. As a result, FBXO24 inhibits LSD1-induced tumorigenesis and functions as a tumor suppressor in breast cancer cells. Moreover, FBXO24 exhibits an inverse correlation with LSD1 and is associated with a favorable prognosis in breast cancer patient samples. Taken together, our study uncovers the significant role of FBXO24 in impeding breast tumor progression by targeting LSD1 for degradation.

Original languageEnglish
Pages (from-to)1303-1316
Number of pages14
JournalMolecular Cancer Research
Volume21
Issue number12
DOIs
StatePublished - Jan 1 2023

Bibliographical note

Publisher Copyright:
© 2023 American Association for Cancer Research.

ASJC Scopus subject areas

  • General Medicine

Fingerprint

Dive into the research topics of 'FBXO24 Suppresses Breast Cancer Tumorigenesis by Targeting LSD1 for Ubiquitination'. Together they form a unique fingerprint.

Cite this