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Related Concept Videos

Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
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Nucleotide Excision Repair01:38

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DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
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Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
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In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
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Nonradioactive Assay to Measure Polynucleotide Phosphorylation of Small Nucleotide Substrates
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Effect of phosphorylation and single nucleotide polymorphisms on caspase substrates processing.

Sonu Kumar1,2, Piotr Cieplak3

  • 1SBP Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.

Apoptosis : an International Journal on Programmed Cell Death
|February 18, 2018
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Summary

Phosphorylation and genetic variations (SNPs) significantly impact caspase activity, influencing protein cleavage. Understanding these effects is crucial for linking aberrant proteolysis to diseases.

Keywords:
ApoptosisCaspase substratesCross-talk between posttranslational modificationsPhosphorylationPosttranslational modification of proteinsSNPs

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Posttranslational modifications, including phosphorylation and proteolysis, regulate vital cellular processes like apoptosis and signal transduction.
  • Cross-talk between proteases (caspases) and kinases is increasingly recognized, with kinases modulating caspase activity.
  • Single nucleotide polymorphisms (SNPs) can alter protein cleavage sites, potentially leading to disease.

Purpose of the Study:

  • To investigate the impact of phosphorylation and SNPs on human caspase proteolytic events.
  • To predict how these modifications affect caspase substrate cleavage using computational methods.

Main Methods:

  • Utilized Random Forest caspases' substrates prediction method (CaspDB).
  • Employed molecular dynamics free energy simulations.
  • Analyzed data from CASBAH and Degrabase databases.

Main Results:

  • Phosphorylation can positively or negatively regulate caspase cleavage, with effects varying by position relative to the cleavage site.
  • Phosphorylation at P1', P2, and P2' positions was found to be detrimental to proteolytic efficiency.
  • Identified SNPs in 11 caspase substrates that abolish cleavage sites at the P1 position.

Conclusions:

  • Phosphorylation and SNPs are key regulators of caspase-mediated proteolysis.
  • Findings provide insights into the molecular mechanisms underlying diseases associated with aberrant proteolysis.
  • This study highlights the interplay between genetic variation, protein modification, and enzyme activity.