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Characterization of alternatively spliced products and tissue-specific isoforms of USP28 and USP25
Valero Gils, Rebeca; Bayés Colomer, Mònica; Sánchez-Font, Ma. Francisca; Gonzàlez-Angulo, Olga; Gonzàlez-Duarte, Roser; Marfany i Nadal, Gemma
Universitat de Barcelona
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.
04-05-2010
Biologia cel·lular
Genètica molecular
Medicina
Neurobiologia
Cell biology
Molecular biology
Medicine
Neurobiology
cc-by, (c) Valero et al., 2001
http://creativecommons.org/licenses/by/2.0/
Artículo
BioMed Central
         

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