Characterization of alternatively spliced products and tissue-specific isoforms of USP28 and USP25

Background The ubiquitin-dependent protein degradation pathway is essential for the proteolysis of intracellular proteins and peptides. Deubiquitinating enzymes constitute a complex protein family involved in a multitude of cellular processes. The ubiquitin-specific proteases (UBP) are a group of enzymes whose predicted function is to reverse the ubiquitinating reaction by removing ubiquitin from a large variety of substrates. We have lately reported the characterization of human USP25, a specific-ubiquitin protease gene at 21q11.2, with a specific pattern of expression in murine fetal brains and adult testis. Results Database homology searches at the DNA and protein levels and cDNA library screenings led to the identification of a new UBP member in the human genome, named USP28, at 11q23. This novel gene showed preferential expression in heart and muscle. Moreover, cDNA, expressed sequence tag and RT-PCR analyses provided evidence for alternatively spliced products and tissue-specific isoforms. Concerning function, USP25 overexpression in Down syndrome fetal brains was shown by real-time PCR. Conclusions On the basis of the genomic and protein sequence as well as the functional data, USP28 and USP25 establish a new subfamily of deubiquitinating enzymes. Both genes have alternatively spliced exons that could generate protein isoforms with distinct tissue-specific activity. The overexpression of USP25 in Down syndrome fetal brains supports the gene-dosage effects suggested for other UBP members related to aneuploidy syndromes.

[
  "009:25"
]

{
  "fn": "NIH",
  "@type": "vcard:Contact",
  "hasEmail": "mailto:info@nih.gov"
}

[
  {
    "@type": "dcat:Distribution",
    "title": "Official Government Data Source",
    "mediaType": "text/html",
    "description": "Visit the original government dataset for complete information, documentation, and data access.",
    "downloadURL": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC57798/"
  }
]

[
  "alternative-splicing",
  "deubiquitinating-enzymes",
  "nih",
  "usp25-expression",
  "usp28-isoforms"
]

[
  "009:033"
]

{
  "name": "National Institutes of Health",
  "@type": "org:Organization"
}

[
  "NIH"
]