PLOD1

更新于：2025-05-07

基本信息

别名

LH1、LLH、Lysyl hydroxylase 1

+ [3]

简介

Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linkling of collagen fibrils (By similarity). Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens (PubMed:10686424, PubMed:15854030, PubMed:8621606). These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links (Probable).

关联

靶点

PLOD1

作用机制

PLOD1 modulators

在研机构

UMass Chan Medical School

原研机构

UMass Chan Medical School

在研适应症

Ehlers-Danlos综合征

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PLOD1 相关的临床结果

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100 项与 PLOD1 相关的转化医学

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0 项与 PLOD1 相关的专利（医药）

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641

项与 PLOD1 相关的文献（医药）

2025-04-01·Biochimica et Biophysica Acta (BBA) - Bioenergetics

Structural integrity and near-infrared absorption of the LH1 complex of Thermochromatium tepidum: Influence from the C-terminal lysine residues of LH1 α-polypeptide

Article

作者: Yan, Yi-Hao ; Zhang, Jian-Ping ; Yu, Long-Jiang ; Zou, Mei-Juan ; Li, Yu-Qian

The light-harvesting complex 1-reaction center (LH1-RC) photosystem of the thermophilic purple sulfur bacterium Thermochromatium (Tch.) tepidum exhibits a near-infrared LH1-Q_y absorption band at 915 nm as regulated by binding calcium ions (Ca²⁺). To further explore the possible involvement of the C-terminal lysine residues of the LH1 α-polypeptide, we have genetically engineered a Rhodospirillum rubrum mutant strain to yield the site-directed modifications of the terminal α-Lys60 and α-Lys61 residues of Tch. tepidum LH1 α-polypeptide. Four of the LH1 mutants exhibit a subtle blue shift of 3 nm upon deletion or substitution of the lysine residues, however, they display over 40 nm blue shifts upon Ca²⁺ removal by ethylene diamine tetraacetic acid (EDTA) treatment. Spectral properties of native Tch. tepidum LH1-RC, the LH1-only, and the mutant LH1-only complexes are compared on a structural basis, which allows us to conclude that the C-terminal lysine residues and the Ca²⁺ binding synergistically affect the structural integrity and the LH1-Q_y spectral shift. This work demonstrates a methodology for the genetic manipulation of photosynthetic proteins lacking mutagenesis information, and may shed light on understanding the detailed structural factors involved in tuning the LH1-Q_y absorption.

2025-04-01·Archives of Biochemistry and Biophysics

A novel tRNA-Derived Fragment, tRF-20-M0NK5Y93 inhibits the malignant progression of non-small cell lung cancer by mediating PLOD1

Article

作者: Chen, Xiaojie ; Chen, Dong ; Chen, Qin ; Wu, Fengjie ; Wu, Lixin

OBJECTIVENon-small cell lung cancer (NSCLC) constitutes a common malignant tumor characterized by substantial mortality rates. Transfer RNA (tRNA)-derived small RNAs (tsRNAs) have been implicated in the progression of various cancers, including NSCLC. However, to date, only a limited number of tsRNAs have been reported to be involved in the development of NSCLC. Hence, the present study aimed to investigate the potential roles of tsRNAs in the progression of NSCLC.MATERIALS AND METHODSA total of forty-six patients with NSCLC who underwent surgical resection were enrolled in this study. The expression patterns of tRNA-derived fragments (tRFs) in tumor and normal tissues of 6 NSCLC cases were investigated using RNA-sequencing assay. Cell viability, proliferation capacity, and migratory ability were measured utilizing the CCK-8, colony formation, and Transwell assays, respectively. Furthermore, cell apoptosis was evaluated by applying flow cytometry. The xenograft tumor model was constructed to observe tumor growth. The relationship between tRF-20-M0NK5Y93 and PLOD1 was clarified using the luciferase and RIP assays.RESULTSThe RNA-sequencing assay revealed a significant decrease in the expression of tRF-20-M0NK5Y93 in tumor tissues. In line with this finding, qRT-PCR analysis further confirmed a meaningful downregulation of tRF-20-M0NK5Y93 in 46 patient samples with NSCLC. Importantly, this downregulated expression was strongly correlated with reduced patient survival. Additionally, overexpression of tRF-20-M0NK5Y93 was found to inhibit the proliferation and migration capabilities of NSCLC cells, leading to suppressed tumor growth and accelerated apoptosis. Furthermore, tRF-20-M0NK5Y93 was capable of binding to PLOD1, thereby negatively regulating its expression. Notably, the restoration of PLOD1 expression was able to counteract the inhibitory effects of enforced tRF-20-M0NK5Y93 on NSCLC cell proliferation, migration, and apoptosis.CONCLUSIONThe expression level of tRF-20-M0NK5Y93 was found to be decreased in NSCLC. Overexpressed tRF-20-M0NK5Y93 exhibited inhibitory effects on NSCLC cell proliferation and migration, accelerated apoptosis, and suppressed tumor growth by targeting PLOD1. These findings highlight tRF-20-M0NK5Y93 as a promising target for NSCLC therapy.

2025-04-01·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Increasing collagen synthesis in fibroblasts: The roles of PCL microspheres and the SAMD11–PLOD1 axis in skin rejuvenation

Article

作者: Cao, Mibu ; Zhang, Youliang ; Ge, Yuanlong ; Tao, Li ; Luo, Shengkang ; Zou, Ying ; Zhou, Lingcong ; Wu, Shu ; Zhou, Haoxian

The degradation of extracellular matrix proteins such as collagen and elastin with aging leads to skin sagging. Polycaprolactone (PCL) microspheres are used as facial fillers because of their ability to provide volume, biodegradability, and collagen-stimulating properties. The direct biological effects of PCL microspheres on fibroblasts, particularly in stimulating sustained collagen production, require further investigation. We detected the safety and effect of PCL microspheres on human fibroblasts and investigated new collagen synthesis and the thickness of C57BL/6 mouse skin. Through an RNA-seq analysis of differentially expressed genes, we identified a key regulator of collagen production in PCL-stimulated fibroblasts. Our research revealed that PCL microspheres are safe for human fibroblasts, promoting their proliferation and increasing new collagen synthesis and skin thickness. We identified sterile alpha motif domain containing 11 (SAMD11) as a key regulator of collagen production in PCLstimulated fibroblasts through an RNA-seq analysis. By increasing SAMD11 expression, PCL microspheres increase collagen synthesis and rejuvenate skin through the upregulation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1). This study elucidates the mechanism by which SAMD11 regulates the effects of PCL microspheres as collagen stimulants for skin rejuvenation, providing a foundation for the future development and refinement of similar materials.

项与 PLOD1 相关的新闻（医药）

2023-03-13

·生物谷

Mol Cancer：我国科学家揭示赖氨酸羟化酶1促进肝癌细胞和胰腺癌细胞迁移和转移

癌症转移是导致癌症相关死亡的一个主要原因。在一项新的研究中，来自中国香港城市大学和重庆医科大学第二附属医院的研究人员发现了一种引发肝癌细胞和胰腺癌细胞迁移和转移并且与患者的生存时间缩短有关的蛋白。癌症转移是导致癌症相关死亡的一个主要原因。在一项新的研究中，来自中国香港城市大学和重庆医科大学第二附属医院的研究人员发现了一种引发肝癌细胞和胰腺癌细胞迁移和转移并且与患者的生存时间缩短有关的蛋白。这些研究结果经体外和体内模型验证，并有临床数据支持，有望为癌症治疗提供一种新的潜在靶标。相关研究结果近期发表在Molecular Cancer期刊上，论文标题为“Lysyl hydroxylase LH1 promotes confined migration and metastasis of cancer cells by stabilizing Septin2 to enhance actin network”。论文共同通讯作者、香港城市大学生物医学讲座教授Michael Yang Mengsu博士说，“癌症转移是一个复杂的过程。众所周知，肿瘤和周围组织的硬化程度随着肿瘤的生长而增加，这在多种癌症类型中为肿瘤细胞的迁移和转移创造了有限空间（confined space），即通道状的孔隙轨道。但这种在有限空间中迁移（下称受限迁移）的机制仍不清楚。我们的目标是深入研究癌症转移机制，并确定与之相关的新基因和蛋白。” 作为最常见的肝癌类型，肝细胞癌（HCC）是世界上第二大癌症死因。胰腺导管腺癌（PDAC）是另一种高度侵袭性的癌症，五年生存率不到10%。这两种癌症都具有实体瘤的典型特征，即胞外基质（ECM）沉积过多，含有使癌细胞迁移的有限孔隙或通道状轨道。因此，这些作者选择了这两种不同的癌症类型作为研究对象。开发研究迁移机制的方法这些作者首先收集了分别来自153名和63名患者的HCC和PDAC样本进行分析。这些作者在手术前没有接受化疗或放疗。他们还从美国国家卫生研究院获得了人类肝癌和胰腺癌细胞系。 Yang教授解释说，“主要的挑战是模拟复杂的癌症微环境。但目前缺乏关于细胞在有限环境中迁移的研究模型。因此，我们开发了一系列多维平台以及二维和三维体外和体内模型，以全面研究细胞迁移过程。” 这些平台和模型包括用于研究单个细胞和集体细胞迁移的微流控芯片，以及用于模拟体内环境的三维侵袭试验的不同硬度的水凝胶。他们还利用下一代测序（NGS）和液相色谱-质谱（LC-MS）来确定癌症组织中差异表达的基因和蛋白。 LH1是促进HCC和PDAC细胞受限迁移的一种关键因子基于下一代测序的转录组分析和基于LC-MS的蛋白质组分析，这些作者确定了一种名为赖氨酸羟化酶1（lysyl hydroxylase 1, LH1）的蛋白是HCC组织中最明显过表达的蛋白之一。他们开发的微流控芯片和三维侵袭模型展示了LH1在多维度上促进受限迁移的能力，包括HCC和PDAC细胞的迁移速度和侵袭能力。这些作用可以通过敲除LH1的表达而被抑制。 LH1高表达与HCC和PDAC患者预后不良相关。图片来自Molecular Cancer, 2023, doi:10.1186/s12943-023-01727-9。他们还证实LH1可以结合并稳定Septin2（SEPT2）以增强肌动蛋白网络的形成；作为一种蛋白，SEPT2在为细胞的高机械迁移需求做准备时起着至关重要的作用。肌动蛋白网络是细胞骨架中最有活力的元素，分布在整个细胞质中，并控制着细胞的力学和运动。因此，增强肌动蛋白网络的形成可以促进HCC和PDAC细胞的受限迁移和转移。 LH1高表达水平导致癌症患者预后不良这些作者还分析了LH1与HCC和PDAC患者的预后（即疾病的发展和复发的机会）之间的相关性。临床样本显示LH1表达较高伴随着预后不佳的患者的生存率只有LH1低表达的患者的一半。此外，LH1高表达的HCC和PDAC患者从确诊到死亡的总生存时间较短，分别为39和17个月，而LH1水平较低的患者则为86和22个月。另外，LH1高表达的HCC和PDAC患者从初次治疗到疾病复发的无病生存时间分别为11.5和14个月，而LH1水平较低的患者为41和19个月。 Yang教授说，“我们开发的平台和方法为研究癌细胞的受限迁移提供了一种独特的方法。我们证实了LH1通过稳定SEPT2促进癌细胞的受限迁移和转移，并且高水平的LH1与HCC和PDAC患者的不良预后有关。这些发现有望为癌症诊断和药物开发提供一种潜在的新靶标。”（生物谷 Bioon.com）参考资料： Zihan Yang et al. Lysyl hydroxylase LH1 promotes confined migration and metastasis of cancer cells by stabilizing Septin2 to enhance actin network. Molecular Cancer, 2023, doi:10.1186/s12943-023-01727-9.