Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases.
We have identified and cloned 22 human cDNAs encoding novel members of the ubiquitin-specific protease (USP) family. Eighteen of the identified proteins contain all structural features characteristic of these cysteine proteinases, whereas four of them have been classified as non-peptidase homologues. Northern blot analysis demonstrated that the identified USPs are broadly and differentially distributed in human tissues, some of them being especially abundant in skeletal muscle or testis. Enzymatic studies performed with the identified USPs revealed that at least twelve of them are deubiquitylating enzymes based on their ability to cleave ubiquitin from a ubiquitin-beta-galactosidase fusion protein. These results provide additional evidence of the extreme complexity and diversity of the USP proteolytic system in human tissues and open the possibility to explore the relevance of their multiple components in the regulation of ubiquitin-mediated pathways in normal and pathological functions.
Quesada
Víctor
V
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Spain.
Díaz-Perales
Araceli
A
Gutiérrez-Fernández
Ana
A
Garabaya
Cecilia
C
Cal
Santiago
S
López-Otín
Carlos
C
D000595:Amino Acid Sequence; D003001:Cloning, Molecular / Q000379:methods*; D046508:Culture Techniques; D010450:Endopeptidases / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes; D008969:Molecular Sequence Data; D009928:Organ Specificity; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D064570:Ubiquitin-Specific Proteases
D007527:Isoenzymes; D010450:Endopeptidases; D064570:Ubiquitin-Specific Proteases