JTB Human
Description
Introduction to JTB Human
The Jumping Translocation Breakpoint (JTB) protein, encoded by the JTB gene (chromosome 1q21), is a transmembrane protein with diverse roles in cellular processes and cancer progression. Initially identified through its involvement in chromosomal translocations, JTB has been implicated in breast, prostate, and liver cancers, functioning either as a tumor suppressor or oncogene depending on the context . Its molecular weight is approximately 16.4 kDa, comprising a 30-amino acid signal sequence, a 75-amino acid extracellular domain (rich in cysteine), a 21-amino acid transmembrane domain, and a 20-amino acid intracellular domain .
Biological Functions
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Mitosis and Cytokinesis: Critical for spindle assembly, chromatin-induced microtubule stabilization, and cell division .
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Apoptosis Regulation: Inhibits TGFB1-induced apoptosis and modulates mitochondrial membrane potential .
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Metabolic Reprogramming: Linked to fatty acid synthesis, glycolysis, and iron metabolism in cancer cells .
Role in Cancer Pathogenesis
JTB’s dual role as an oncogene or tumor suppressor varies by cancer type:
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Overexpression in Breast Cancer:
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Downregulation in Prostate Cancer:
Proteomic Insights
Recent studies using MCF7 breast cancer cells with JTB overexpression or silencing identified key differentially expressed proteins (DEPs):
| Condition | Upregulated Proteins | Downregulated Proteins | Associated Pathways |
|---|---|---|---|
| JTB Overexpression | ACTN1, HSPA1A, EZR, COL3A1, COL11A1, FASN | TUBB4B, PSMB9, SLC9AR1, ANXA4 | EMT, Mitotic Spindle, Fatty Acid Metabolism |
| JTB Silencing | HSPB1, HSPA4, EEF2, PCK1, IFIT1 | RPS5, YWHAZ, YWHAE | UPR, Interferon Signaling, ERK/MAPK |
Data sourced from in-gel and in-solution proteomic analyses .
Epithelial-to-Mesenchymal Transition (EMT)
JTB overexpression drives EMT via:
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Cytoskeletal Remodeling: Upregulation of ACTN1, FLNA, and PFN2 (actin-binding proteins) .
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ECM Remodeling: COL3A1 and COL11A1 (collagen synthesis) promote metastasis .
Metabolic Reprogramming
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Lipid Biosynthesis: FASN (fatty acid synthase) and PCK1/PCK2 (gluconeogenesis enzymes) enhance cancer cell proliferation .
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Oxidative Stress Management: PRDX3 (peroxiredoxin) mitigates reactive oxygen species (ROS) .
Therapeutic Resistance
JTB dysregulation correlates with:
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Hormone Therapy Resistance: Upregulation of HSPA1A and HSP90A (chaperones for estrogen receptors) .
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Immune Evasion: Downregulation of PSMB9 (proteasome subunit) and SLC9AR1 (ion transport) .
Clinical and Research Implications
Product Specs
Q&A
What is the Jumping Translocation Breakpoint (JTB) gene, and why is it significant in research?
The JTB gene, located on human chromosome 1 at q21, encodes a protein implicated in various cellular processes, including mitotic spindle assembly, epithelial-to-mesenchymal transition (EMT), and estrogen response pathways. Its role as either a tumor suppressor or oncogene in different malignancies, such as breast cancer, highlights its importance in understanding tumorigenesis and cellular regulation . The protein's ubiquitous expression across tissues and its evolutionary conservation among species underscore its fundamental biological significance .
How does JTB expression vary across tissues and cell types?
JTB expression is detected in numerous tissues, including the kidney, lung, stomach, colon, and various cancer cell lines like MCF7 breast cancer cells. At the subcellular level, it localizes to membranes, mitochondria, and the microtubule cytoskeleton during mitosis . High-resolution imaging and RNA sequencing data confirm its differential expression patterns at both mRNA and protein levels .
What are the key considerations when designing experiments to study JTB function?
When studying JTB function, researchers must consider:
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Cell Line Selection: Use cell lines relevant to the biological question (e.g., MCF7 for breast cancer studies).
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Overexpression or Knockdown Models: Employ techniques such as transfection with tagged vectors (e.g., HA, His, FLAG) for overexpression or siRNA/CRISPR for knockdown experiments.
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Proteomic Analysis: Utilize tools like nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS) to analyze protein interactions and dysregulation patterns .
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Pathway Analysis: Perform Gene Set Enrichment Analysis (GSEA) to identify biological processes associated with JTB dysregulation .
How can proteomics be used to investigate JTB's role in cancer?
Proteomics allows for the identification of proteins that interact with or are regulated by JTB. For instance:
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Proteins extracted from cells with altered JTB expression can be separated via SDS-PAGE.
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Peptides are analyzed using nanoLC-MS/MS to detect changes in protein abundance.
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GSEA can reveal enriched pathways such as mitotic spindle assembly or EMT, providing insights into how JTB contributes to tumorigenesis .
What statistical methods are recommended for analyzing JTB-related data?
Statistical rigor is crucial in JTB research:
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Use paired Student’s t-tests for comparing means between control and experimental groups.
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Apply false discovery rate (FDR) thresholds (<0.25) in GSEA to determine pathway significance.
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Ensure biological replicates (minimum of three) for robust data interpretation .
How can researchers address contradictions in data regarding JTB's oncogenic vs. tumor-suppressive roles?
Contradictions can arise due to differences in experimental conditions or cellular contexts:
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Compare findings across multiple cell lines and tissue types.
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Investigate post-translational modifications or interaction partners that may influence JTB's function.
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Integrate transcriptomic and proteomic data to build a comprehensive understanding of its role .
Which pathways are significantly upregulated by JTB overexpression?
Overexpression of JTB has been linked to several key pathways:
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Mitotic Spindle Assembly: Essential for accurate chromosome segregation during cell division.
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Epithelial-to-Mesenchymal Transition (EMT): A process critical for cancer metastasis.
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Estrogen Response (Early and Late): Indicates a potential role in hormone-responsive cancers like breast cancer .
How does JTB influence epithelial-to-mesenchymal transition (EMT)?
JTB upregulation enhances EMT by promoting cellular changes that increase motility and invasiveness—hallmarks of metastatic cancer cells. Proteomic studies have identified specific proteins involved in this transition that are regulated by JTB .
How can researchers integrate multi-omics data to study JTB?
Multi-omics approaches combine data from genomics, transcriptomics, proteomics, and metabolomics:
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Genomics: Identify mutations or structural variations involving the JTB locus.
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Transcriptomics: Analyze differential gene expression using RNA-seq.
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Proteomics: Quantify protein abundance and interaction networks.
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Metabolomics: Explore metabolic changes associated with altered JTB activity .
What tools are available for visualizing JTB-related pathways?
Tools such as Cytoscape for network visualization and GSEA for pathway enrichment analysis are invaluable:
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Cytoscape enables the creation of interaction maps linking JTB to other proteins.
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GSEA provides statistical summaries of pathway activations based on experimental data .
What ethical guidelines should be followed when conducting research on human-derived samples?
Researchers must adhere to ethical standards such as obtaining informed consent from donors of biological samples and ensuring compliance with institutional review board (IRB) protocols.
How can data sharing be facilitated while maintaining participant confidentiality?
Data sharing should align with FAIR principles (Findable, Accessible, Interoperable, Reusable). De-identify datasets before sharing and use secure repositories like the Gene Expression Omnibus (GEO) or ProteomeXchange .
Product Science Overview
Jumping translocations are rare chromosomal rearrangements characterized by the re-localization of one donor chromosome to multiple recipient chromosomes . These translocations result in the amplification of specific chromosomal segments that jump to various telomeres . JTs have been reported in neoplasms and constitutional chromosome abnormalities, but they are particularly rare in neoplastic diseases .
JTB is expressed in all normal human tissues but is overexpressed or underexpressed in many malignant counterparts . It plays a crucial role in the regulation of cell proliferation and is required for normal cytokinesis during mitosis . JTB may also be a component of the chromosomal passenger complex (CPC), which is essential for correct chromosome alignment and segregation during cell division .
Jumping translocations involve the fusion of the break-off donor chromosome segment to telomeric or interstitial regions of recipient chromosomes, forming different chromosomal patterns . For example, jumping translocations involving the 1q12–21 segment are nonrandomly involved in multiple myeloma and malignant lymphoproliferative disorders . These translocations are associated with a high risk of transformation to acute myeloid leukemia, resistance to chemotherapy, and poor survival rates .
Recombinant human JTB protein is often used in research to study its role in cell proliferation and cancer. The protein is typically expressed in HEK293 cells and purified for various experimental applications . Understanding the function and mechanism of JTB can provide insights into the development of targeted therapies for cancers involving jumping translocations.
