HOPX Human
Description
Gene Structure and Protein Characteristics
The HOPX gene is located on human chromosome 4q12 and encodes a nuclear protein with three α-helical structures resembling a classical homeodomain fold . Key features include:
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Isoforms: Three protein isoforms (α, β, γ) generated via alternative splicing, with the β isoform containing a CpG island promoter frequently silenced in cancers .
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DNA-binding deficiency: Lacks conserved residues required for DNA interaction, relying instead on protein-protein interactions to modulate transcription .
Biological Functions
HOPX serves as a master regulator in development and tissue homeostasis:
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Cardiac development: Interacts with serum response factor (SRF) and histone deacetylases (HDACs) to regulate cardiomyocyte proliferation and differentiation .
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Stem cell maintenance: Expressed in adult stem cell niches (intestinal crypts, hair follicles, lung) and promotes quiescence in label-retaining stem cells .
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Apoptosis and differentiation: Controls keratinocyte differentiation via PKC signaling and radial glial cell apoptosis in the hippocampus .
Role in Cancer
HOPX is widely recognized as a tumor suppressor, with silencing observed in multiple cancers due to promoter hypermethylation :
Mechanistically, HOPX suppresses oncogenic pathways by:
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Inhibiting Wnt/β-catenin signaling in squamous cell carcinoma .
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Enhancing apoptosis and senescence via p53 and p16 pathways .
Key Research Findings
Recent studies highlight HOPX’s multifaceted roles:
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HNSCC: Ectopic HOPX expression in oral squamous cell carcinoma suppresses proliferation and invasion by downregulating genes involved in DNA damage response and adhesion .
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Hematopoiesis: HOPX is enriched in hematopoietic stem cells (HSCs) but predicts adverse outcomes in AML, indicating context-dependent functions .
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Aging: Elevated HOPX in aged CD8+ T cells correlates with reduced proliferation, implicating it in immunosenescence .
Future Directions
Unresolved questions include:
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Isoform-specific functions and binding partners in different tissues.
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Mechanisms of HOPX-mediated chromatin remodeling.
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Clinical trials evaluating HOPX reactivation in combination with existing therapies.
Product Specs
Product Science Overview
The HOP homeobox (HOPX) gene, also known as NECC1, LAGY, or OB1, is a member of the homeobox gene family. Homeobox genes are characterized by the possession of a particular DNA sequence, the homeobox, which encodes a recognizable although very variable protein domain, the homeodomain . The homeodomain is a 61-amino-acid domain that acts by recognizing and binding sequence-specific DNA motifs .
HOPX was initially identified as a gene essential for cardiac growth and development . It is the smallest homeodomain protein and lacks certain conserved residues required for DNA binding . Instead, HOPX functions as an adapter protein to mediate transcription by interacting with other transcription factors such as serum response factor (SRF) .
In normal tissues, HOPX plays a critical role in regulating physiological functions. It is involved in various developmental processes, including embryogenesis and organogenesis . HOPX’s interaction with SRF and other substances helps regulate the differentiation phenotype and maintain normal tissue function .
HOPX has been identified as a tumor suppressor gene candidate, characterized by tumor-specific promoter DNA hypermethylation in human cancers . This hypermethylation leads to gene silencing, which can inhibit the aggressive phenotypes of tumors . In pancreatic cancer, for example, HOPX promoter hypermethylation is significantly higher in tumor tissues compared to normal tissues . This hypermethylation is associated with reduced expression of HOPX in pancreatic cancer cells, contributing to the aggressive nature of the disease .
The tumor suppressive role of HOPX makes it a potential target for cancer therapy. Understanding the mechanisms by which HOPX regulates tumor progression could lead to novel therapeutic strategies . Additionally, the unique expression patterns of HOPX in different tissues and its involvement in various physiological processes highlight its importance in both normal and pathological conditions .
