LSD1是一个重要的染色质调节因子，通过去甲基化H3K4me1/2而发挥致癌基因的功能。LSD1的稳定性由一个复杂且精细的过程控制，其中涉及泛素化和去泛素化。几种去泛素酶保持LSD1蛋白的水平。然而，LSD1降解的精确机制尚不清楚，这可能减轻其致癌功能。为了更好地理解LSD1的降解，我们进行了一项针对所有人类SCF家族E3连接酶的无偏siRNA筛选。我们的筛选发现FBXO24是一个真正的E3连接酶，可以泛素化和降解LSD1。结果表明，FBXO24抑制了LSD1诱导的肿瘤发生，并在乳腺癌细胞中作为肿瘤抑制基因发挥作用。此外，FBXO24与LSD1呈相反的相关性，并与乳腺癌患者样本的良好预后相关。综上所述，我们的研究揭示了FBXO24在通过降解LSD1阻碍乳腺肿瘤进展中的重要作用。意义：我们的研究全面描述了FBXO24在通过降解LSD1阻碍乳腺肿瘤进展中的重要作用。

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. Implications: Our study provides comprehensive characterization of the significant role of FBXO24 in impeding breast tumor progression by targeting LSD1 for degradation.