LOX

What is LOX protein?

LOX gene (lysyl oxidase) is a protein coding gene which situated on the long arm of chromosome 5 at locus 5q23. This gene encodes a member of the lysyl oxidase family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate a regulatory propeptide and the mature enzyme. The copper-dependent amine oxidase activity of this enzyme functions in the crosslinking of collagens and elastin, while the propeptide may play a role in tumor suppression. The LOX protein is consisted of 417 amino acids and LOX molecular weight is approximately 46.9 kDa.

What is the function of LOX protein?

Lysyl oxidase (LOX) is a copper-dependent enzyme that plays a catalytic role in the assembly of the extracellular matrix (ECM) and is essential for cell fate, cell communication during differentiation and development by promoting intramolecular and intermolecular crosslinking of ECM components. LOX not only plays a role in ECM, but is also involved in multiple biological processes, including epithelial-mesenchymal transition (EMT) and transcriptional regulation, especially after hypoxic stress. LOX has been shown to be active in glioblastoma, diabetic neovascularization, osteogenic differentiation, bone stroma formation, ligament remodeling, polycystic ovary syndrome, rupture of fetal membrane, and tumor progression and metastasis. LOX has complex cell - and tissue-specific interactions with multiple signaling pathways, not only as regulatory targets, but also as active participants, including LOX-mediated changes in cell surface receptor function and mutual regulatory activity within the signaling ring.

Fig1. Role of LOX-1 in vascular smooth muscle cells contributing to atherosclerosis. (Ajoe John Kattoor, 2019)

LOX related signaling pathway

Lysyl oxidase (LOX) is a copper-dependent enzyme that plays a key role in the assembly and biological function of the extracellular matrix (ECM). LOX is essential for cell adhesion, proliferation, differentiation, and migration by catalyzing the cross-linking of ECM components. LOX is also involved in the regulation of several signaling pathways, such as epidermal growth factor receptor (EGFR), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β). These signaling pathways are closely related to tumor progression, angiogenesis, cell migration and tissue repair.

LOX related diseases

The LOX protein family plays a role in a variety of diseases, particularly in relation to tumor development, tissue fibrosis, and cardiovascular disease. By catalyzing the cross-linking of collagen and elastin, LOX affects the structure and function of extracellular matrix, and then participates in the regulation of cell adhesion, migration and signal transduction. Abnormal expression of LOX has been linked to the development of multiple cancers, including breast, lung, liver, and prostate cancers. In cardiovascular disease, increased expression of LOX family members is associated with diseases such as atherosclerosis, hypertension, and diabetes. LOX has also been implicated in neurodegenerative diseases, fibrotic diseases, and inflammatory responses.

Bioapplications of LOX

LOX is a copper-dependent enzyme that plays a key role in the crosslinking and maturation of the extracellular matrix (ECM) and is essential for maintaining tissue structure and function. rhLOX can be used to study the assembly and remodeling of ECM and how these processes change in disease. For example, LOX's role in the tumor microenvironment makes it a potential target for cancer therapy, particularly in breast and lung cancer. In addition, the activity of LOX in fibrotic diseases, cardiovascular diseases, and neurodegenerative diseases is also of interest to researchers. rhLOX can also be used as a research tool to develop and test small molecule inhibitors or antibodies against LOX that may be beneficial in treating related diseases. In the field of biotechnology, rhLOX may be used to develop new diagnostic methods or as part of drug delivery systems.

Case Study 1: Shin Iwamoto, 2009

LOX-1, a key receptor for oxidized LDL (oxLDL), is central to atherosclerosis and cardiovascular disease development. Researchers developed 53 monoclonal antibodies (mAbs) against human LOX-1 using a phage display technique and chickens immunized with recombinant LOX-1. Most of these mAbs targeted the C-type lectin-like domain essential for oxLDL binding and inhibited this interaction. Notably, two of these mAbs were developed into chicken-human chimeric antibodies, which could potentially serve as therapeutic agents, showing equivalent effects to the original antibodies in blocking oxLDL binding to LOX-1 on CHO cells.

Fig1. Reactivity of rIgY antibodies against rhLOX-1 and delta NECK.

Fig2. Western blot analysis of recombinant chicken antibody and chicken-human chimeric antibody.

Case Study 2: Can Li, 2021

Autophagy, a process for cellular balance, has a complex role in cancer that can vary by context. In esophageal cancer (EC), LOX-1, a scavenger receptor for oxidized LDL, plays a significant role. This study showed that LOX-1 is upregulated in EC and linked to worse patient outcomes. LOX-1 deletion hinders EC growth by promoting autophagic cell death. RACK1, a signal adapter for LOX-1, activates the RAS/MEK/ERK pathway and enhances tumorigenesis. Fucoidan, a sulfated polysaccharide from brown seaweed, binds to LOX-1, targeting it for proteasomal degradation and triggering autophagy-related cell death in EC.

Fig3. Correlations between LOX-1 expression and tumor size, lymph node metastasis (pN), and TNM stage.

Fig4. TE-1 cells transfected with LOX-1 siRNA were applied to phosphokinase antibody array.

LOX has several biochemical functions, for example, copper ion binding,protein binding,protein-lysine 6-oxidase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by LOX itself. We selected most functions LOX had, and list some proteins which have the same functions with LOX. You can find most of the proteins on our site.

LOX has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with LOX here. Most of them are supplied by our site. Hope this information will be useful for your research of LOX.

EFEMP2;PTPRK;FBLN5;ELN;FBN1;GATAD2B;HSPA1A;COL1A1;COL3A1