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.
Valero
R
R
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Av Diagonal 645, 08028 Barcelona, Spain. gemma@porthos.bio.ub.es
Bayés
M
M
Francisca Sánchez-Font
M
M
González-Angulo
O
O
Gonzàlez-Duarte
R
R
Marfany
G
G
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D022821:RNA Splice Sites; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D025801:Ubiquitin / Q000378:metabolism; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases
D020033:Protein Isoforms; D022821:RNA Splice Sites; D012333:RNA, Messenger; C404488:USP25 protein, human; C442902:USP28 protein, human; D025801:Ubiquitin; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases