LMO1 Human

LIM Domain Only 1 Human Recombinant
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Description

Introduction to LMO1 Human

LMO1 (LIM Domain Only 1), also known as Rhombotin-1, is a nuclear transcriptional cofactor encoded by the LMO1 gene located on human chromosome 11 (11p15.4). It belongs to the LIM-only protein family, characterized by two zinc-finger LIM domains that mediate protein-protein interactions . LMO1 functions as a scaffold in transcriptional complexes, regulating gene expression in developmental and pathological contexts. Its dysregulation is implicated in various cancers, including glioma, neuroblastoma, gastric cancer, and lung cancer .

Molecular Structure and Function

LMO1 lacks intrinsic transcriptional activation/repression domains but interacts with transcription factors (e.g., GATA3, TAL1) to modulate gene expression . Key structural and functional features include:

  • Zinc-finger LIM domains: Critical for binding partners like GATA proteins .

  • Tissue-specific expression: Elevated in neural crest-derived cells and tumors .

  • Regulatory polymorphisms: Genetic variants (e.g., rs2168101) influence cancer susceptibility by altering transcription factor binding .

Table 1: Key Molecular Features of LMO1

FeatureDescriptionRelevance
LIM domainsZinc-finger motifs enabling protein interactionsOncogenic partnerships (e.g., GATA3, MYCN)
rs2168101 polymorphismG/T variant in intron 1; G allele linked to neuroblastoma riskDisrupted GATA binding enhances LMO1 expression
NGFR regulationUpstream regulator of NGFR/p75NTR in gliomaActivates NF-κB pathway to drive proliferation/migration

Role in Cancer Pathogenesis

LMO1 exhibits oncogenic roles in multiple cancers, with distinct mechanisms:

Glioma

Table 2: LMO1-Associated Prognostic Features in Glioma

CohortMolecular SubgroupLMO1 ExpressionSurvival OutcomeSource
TCGAIDH-wtHighReduced OS (HR >1.5)
CGGA1p/19q non-codeletionHighPoor prognosis
GSE16011Glioma patientsHighShorter OS

Neuroblastoma

  • Genetic predisposition:

    • rs2168101 G allele increases risk, particularly in high-risk (HR) neuroblastoma .

    • Synergizes with MYCN amplification to drive tumor initiation and progression .

  • Mechanisms:

    • MYCN interaction: LMO1 enhances MYCN’s transcriptional activity, promoting cell proliferation and survival .

Product Specs

Introduction
The LMO1 gene provides instructions for creating the LIM domain only 1 (LMO1) protein, a transcriptional regulator. This protein plays a role in controlling gene activity but lacks a DNA-binding domain. Instead, it features two cysteine-rich LIM domains, which likely facilitate interactions with other proteins, potentially influencing transcription through competition with specific DNA-binding transcription factors.
Description
This product consists of a single, non-glycosylated polypeptide chain of the LMO1 protein (human recombinant) produced in E.Coli. The chain comprises 179 amino acids (1-156 a.a), with a molecular weight of 20.2kDa. A 23 amino acid His-tag is fused to the N-terminus. The protein has undergone purification using proprietary chromatographic techniques.
Physical Appearance
A clear, sterile solution without any color.
Formulation
The LMO1 protein is supplied in a solution (0.25mg/ml) containing 20mM Tris-HCl buffer (pH 8.0), 0.4M UREA, and 10% glycerol.
Stability
For short-term storage (2-4 weeks), the product can be stored at 4°C. For extended storage, freezing at -20°C is recommended. Adding a carrier protein (0.1% HSA or BSA) is advisable for long-term storage. Minimize repeated freezing and thawing.
Purity
The purity level is above 85.0% based on SDS-PAGE analysis.
Synonyms
Rhombotin-1, Cysteine-rich protein TTG-1, LIM domain only protein 1, T-cell translocation protein 1, RBTN1, RHOM1, TTG1, LMO-1, LMO1.
Source
Escherichia Coli.
Amino Acid Sequence
MGSSHHHHHH SSGLVPRGSH MGSMMVLDKE DGVPMLSVQP KGKQKGCAGC NRKIKDRYLL KALDKYWHED CLKCACCDCR LGEVGSTLYT KANLILCRRD YLRLFGTTGN CAACSKLIPA FEMVMRARDN VYHLDCFACQ LCNQRFCVGD KFFLKNNMIL CQMDYEEGQL NGTFESQVQ

Q&A

Basic Questions

  • What is the role of LMO1 in human glioma progression?

    • LMO1 is a nuclear transcription co-regulator that promotes tumor growth, invasion, and migration in gliomas. It regulates the NGFR-NF-kB axis, which enhances glioma malignancy. Experimental studies have shown that silencing LMO1 inhibits these processes both in vitro and in vivo .

  • How can LMO1 expression be used as a prognostic biomarker for glioma?

    • High expression of LMO1 is associated with poor prognosis, particularly in IDH-wild-type and 1p/19q non-codeletion gliomas. Stratifying patients by molecular features such as MGMT methylation and 1p/19q co-deletion improves prognostic accuracy .

  • What experimental techniques are commonly used to study LMO1 in gliomas?

    • Researchers employ RNA sequencing (RNA-Seq), quantitative PCR (qPCR), western blotting, gene set enrichment analysis (GSEA), and immunohistochemistry (IHC) to analyze LMO1 expression and its molecular mechanisms .

  • What is the relationship between LMO1 and NGFR in gliomas?

    • LMO1 positively regulates NGFR mRNA and protein levels, which mediate NF-kB activation. NGFR enhances cell proliferation, migration, and invasion in glioma cells, establishing its role as a downstream effector of LMO1 .

Advanced Research Questions

  • How does the molecular context (e.g., IDH status or 1p/19q co-deletion) affect the prognostic value of LMO1?

    • LMO1’s prognostic significance is amplified when stratified by molecular features such as IDH mutation status or 1p/19q co-deletion. These factors delineate distinct patient subsets with varied clinical outcomes .

  • What experimental designs can be used to validate LMO1 as a therapeutic target?

    • To validate LMO1 as a therapeutic target, researchers can design knockout models using CRISPR/Cas9 or RNA interference (siRNA). Functional assays measuring proliferation, migration, and invasion in glioma cells can confirm its role. Additionally, in vivo studies with nude mice can test tumor growth inhibition upon LMO1 silencing .

  • How does chemoresistance and radioresistance correlate with LMO1 expression?

    • Elevated levels of LMO1 have been linked to increased resistance to chemotherapy and radiotherapy in gliomas. Investigating this relationship requires comparative studies on treated vs untreated cell lines with varying levels of LMO1 expression .

  • What are the challenges in translating findings on LMO1 to clinical applications?

    • Challenges include variability in patient-specific molecular profiles, incomplete understanding of downstream pathways like NGFR-NF-kB, and limited availability of targeted therapies for transcription cofactors like LMO1 .

Methodological Insights

  • How can data contradictions regarding LMO1's role be resolved?

    • Contradictions can be addressed by standardizing experimental conditions across studies, using authenticated cell lines, replicating experiments in diverse genetic backgrounds, and conducting meta-analyses of existing datasets .

  • What are the ethical considerations when studying human glioma tissues for LMO1 research?

    • Ethical considerations include obtaining informed consent from patients for tissue use, adhering to institutional review board guidelines, and ensuring transparency in reporting race/ethnicity or other demographic factors relevant to the study .

  • How can bioinformatics tools enhance research on LMO1?

    • Bioinformatics tools like GSEA can identify pathways regulated by LMO1, while databases such as TCGA or CGGA provide large-scale genomic data for correlation analyses. Computational modeling can predict interactions between LMO1 and other proteins .

  • What statistical models are suitable for analyzing survival data related to LMO1 expression?

    • Cox proportional hazards regression models are commonly used to predict survival outcomes based on gene expression levels like those of LMO1. Nomograms integrating multiple clinical variables provide individualized risk predictions .

Product Science Overview

Introduction

LIM Domain Only 1 (LMO1) is a member of the LIM-only (LMO) family of genes, which encode transcriptional cofactors. These cofactors play a crucial role in regulating gene transcription by acting as key connectors or scaffolds in transcription complexes . The LMO family consists of four members: LMO1, LMO2, LMO3, and LMO4 .

Gene and Protein Structure

The LMO1 gene is located on human chromosome 11p15.4 and is also known as T-cell translocation gene 1 (TTG-1) or rhombotin . The LMO1 protein is characterized by the presence of LIM domains, which are specialized zinc-binding domains that mediate protein-protein interactions . The human recombinant LMO1 protein is typically produced in Escherichia coli (E. coli) and consists of 179 amino acids, with a molecular mass of approximately 20.2 kDa .

Biological Functions

LMO1 functions as a transcriptional cofactor, meaning it does not directly bind to DNA but instead interacts with other transcription factors to regulate gene expression . This protein is involved in various biological processes, including cell differentiation, development, and tumorigenesis . LMO1 has been shown to play a critical oncogenic role in several types of cancers, such as T-cell acute lymphoblastic leukemia, neuroblastoma, gastric cancer, lung cancer, and prostate cancer .

Mechanisms of Action

The oncogenic activity of LMO1 is primarily attributed to its ability to form transcriptional complexes with other proteins, thereby influencing the expression of genes involved in cell proliferation and survival . The molecular mechanisms underlying LMO1’s functions are complex and not fully understood, but they involve interactions with various transcription factors and co-regulators .

Clinical Implications

Given its role in tumorigenesis, LMO1 is a potential target for cancer diagnosis and therapy . Understanding the mechanisms that drive its aberrant activation in cancers could lead to the development of novel therapeutic strategies. Additionally, LMO1’s involvement in non-cancer diseases and developmental processes highlights its broader significance in human biology .

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