NUDT16L1 Human
Description
Biochemical Properties and Enzymatic Activity
NUDT16L1 belongs to the NUDIX (nucleoside diphosphate-linked moiety X) enzyme family, which hydrolyzes substrates like oxidized nucleotides, mRNA caps, and signaling molecules. Key findings include:
Notably, large-scale substrate screens failed to identify canonical NUDIX substrates (e.g., oxidized nucleotides) under standard conditions, suggesting context-dependent activity .
DNA Repair Regulation
NUDT16L1 stabilizes TP53BP1, a key mediator of DNA double-strand break repair. Upon DNA damage, ATM kinase phosphorylates TP53BP1, displacing NUDT16L1 and enabling TP53BP1 recruitment to chromatin .
Neuronal Development
NUDT16L1 regulates axon growth and neuronal cone formation, likely through interactions with RNA-binding proteins .
Environmental Stress Response
Expression of NUDT16L1 is modulated by:
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Chemical exposure: Bisphenol A, cadmium, and doxorubicin alter its mRNA/protein levels .
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Oxidative stress: Upregulated in response to reactive oxygen species (ROS), suggesting a protective role .
Essentiality in Cancer Cells
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Cell Cycle Effects: Depletion in cancer cell lines (e.g., HeLa, U2OS) causes G1 arrest or apoptosis, indicating therapeutic potential .
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Epistatic Interactions: Genetic screens reveal functional redundancy with NUDT10/11, complicating targeted inhibition .
Expression Profiles
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Tissue Distribution: Highly expressed in brain, liver, and testes (BioGPS/HPA datasets) .
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Cancer vs. Normal Tissues: Overexpressed in glioblastoma and colorectal adenocarcinoma (HPA Tissue Protein Expression Profiles) .
Disease Associations
While direct disease links are under investigation, NUDT16L1 is implicated in:
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Cancer: Dysregulation correlates with TP53BP1-dependent repair defects, promoting genomic instability .
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Neurodegeneration: Altered expression in Alzheimer’s disease models (Allen Brain Atlas datasets) .
Open Questions and Future Directions
Product Specs
Product Science Overview
NUDT16L1 is a single, non-glycosylated polypeptide chain consisting of 231 amino acids, with a molecular mass of approximately 25.5 kDa . The human recombinant form of NUDT16L1 is produced in Escherichia coli (E. coli) and is fused with a 20 amino acid His tag at the N-terminus to facilitate purification .
The primary function of NUDT16L1 is to hydrolyze nucleoside diphosphates linked to other moieties, which is crucial for maintaining cellular homeostasis. By breaking down potentially harmful nucleotide derivatives, NUDT16L1 helps to prevent the accumulation of these compounds, which could otherwise lead to cellular damage.
NUDT16L1 plays a significant role in various cellular processes, including:
- DNA Repair: By hydrolyzing damaged nucleotides, NUDT16L1 helps to maintain the integrity of the genetic material.
- Signal Transduction: The enzyme’s activity can influence various signaling pathways by modulating the levels of nucleotide derivatives.
- Metabolic Regulation: NUDT16L1 is involved in the regulation of metabolic processes by controlling the concentration of nucleotides and their derivatives.
The recombinant form of NUDT16L1 is widely used in research to study its enzymatic activity and its role in cellular processes. It is also used to investigate potential therapeutic applications, such as targeting NUDT16L1 for the treatment of diseases associated with nucleotide metabolism disorders.
