已知赖氨酸特异性去甲基化酶1 (LSD1) 通过与CoREST/ 组蛋白去乙酰化酶 (HDAC) 形成抑制蛋白复合物来执行表观遗传调控。 然而，细胞维持LSD1/CoREST复合体完整性的分子机制尚不清楚。 摘要部分. LSD1蛋白经历K63连接的多泛素化。 作者发现，OTUD7B负责K226/277残基处的LSD1去泛素化，从而动态控制LSD1结合伴侣蛋白的特异性和细胞稳态。 OTUD7B缺乏会增加LSD1与K63相关的泛素化，这会破坏LSD1/CoREST复合物的形成并靶向LSD1进行p62介导的 …

2021年5月29日 · OTUD7B is responsible for LSD1 deubiquitination at K226/277 residues, resulting in dynamic control of LSD1 binding partner specificity and cellular homeostasis. OTUD7B deficiency increases K63-linked ubiquitination of LSD1, which disrupts LSD1/CoREST complex formation and targets LSD1 for p62-mediated proteolysis.

2024年4月1日 · LSD1 can remove methyl groups from histone 3 at lysine 4 or lysine 9 (H3K4 or H3K9), resulting in either transcription repression or activation. While the roles of LSD1 in transcriptional regulation are well-established, studies have revealed that LSD1 can also be dynamically regulated by other factors.

Targeting lysine-specific histone demethylase 1A (LSD1) can improve tumor immunogenicity of poorly immu-nogenic tumors, such as non-small cell lung cancer (NSCLC), with elevated T cell infiltration and sensitize tumors to anti-PD-1 therapy. However, the lack of reliable biomarkers limits utilization of LSD1 inhibitors in cancer therapy.

2024年5月17日 · We discovered that Lsd1 protein stability is regulated by ubiquitin-proteasome system (UPS) during fly follicle development. Through genetic and biochemical means, an E3 ligase, Bre1, was identified to mediate Lsd1 protein degradation during follicle cell differentiation.

4 天之前 · Here, we identified TRIM21 as a direct upstream E3 ligase of LSD1, catalyzing its K63-linked ubiquitination, which in turn promoted its interaction with p62, a Ub receptor known to bind to the proteasome and mediate the degradation of K63-ubiquitinated substrate. 43, 51, 52 Furthermore, we demonstrate that TRIM21 controls LSD1 turnover in a ...

2022年9月15日 · Lysine-specific demethylase 1 (LSD1), a first identified histone demethylase, mediates the removal of methyl groups from histones H3K4me1/2 and H3K9me1/2 and plays a crucial role in varieties of cancer progression.

LSD1是转录共抑制复合物CoREST的一个组成部分，该复合物包含接头蛋白 RCOR1 和组蛋白脱乙酰酶 HDAC1 和 HDAC2。 RCOR1直接与HDAC1/2和LSD1相互作用，将两个酶部分桥接成一个蛋白质复合物。 CoREST 的这种双重酶作用被认为对于基因抑制至关重要。 除了在胚胎发生和分化中的重要性之外，LSD1还与发育障碍、炎症性疾病、神经退行性疾病和癌症有关，使其成为一个有吸引力的治疗靶点。 因此，各种LSD1抑制剂已被开发出来，目前正在进行临床试验。 尽 …

We discovered that Lsd1 protein stability is regulated by ubiquitin-proteasome system (UPS) during fly follicle development. Through genetic and biochemical means, an E3 ligase, Bre1, was identified to mediate Lsd1 protein degradation during follicle cell differentiation.

2021年9月16日 · LSD1 is a histone demethylase regulating transcription. The current study reveals a novel function of LSD1 in regulating the activation of RIG-I signaling pathway. LSD1 interacts with RIG-I and promotes RIG-I poly-ubiquitination independent of …