Expression and functional studies of ubiquitin C-terminal hydrolase L1 regulated genes

Deubiquitinating enzymes (DUBs) have been increasingly implicated in regulation of cellular processes, but a functional role for Ubiquitin C-terminal Hydrolases (UCHs), which has been largely relegated to processing of small ubiquitinated peptides, remains unexplored. One member of the UCH family, U...

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Bibliographic Details
Published in:PloS one 2009-08, Vol.4 (8), p.e6764-e6764
Main Authors: Bheda, Anjali, Shackelford, Julia, Pagano, Joseph S
Format: Article
Language:English
Subjects:
Analysis
Antigens
Apoptosis
Base Sequence
Cell adhesion & migration
Cell Biology
Cell Biology/Gene Expression
Cell Cycle
Cell Line
Cell lines
Cell Movement
Cell Proliferation
Computational Biology
Data processing
DNA microarrays
DNA Primers
Esophagus
Gene expression
Gene Expression Regulation
Genes
Humans
Hydrolase
Hydrolases
Lung cancer
Medical prognosis
Metastasis
Molecular Biology/Bioinformatics
Mutation
Oligonucleotide Array Sequence Analysis
Oncology
Peptides
Protein expression
Protein gene product 9.5
Proteins
Reverse Transcriptase Polymerase Chain Reaction
RNA-mediated interference
Transcription factors
Tumorigenesis
Ubiquitin
Ubiquitin Thiolesterase - physiology
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Summary:Deubiquitinating enzymes (DUBs) have been increasingly implicated in regulation of cellular processes, but a functional role for Ubiquitin C-terminal Hydrolases (UCHs), which has been largely relegated to processing of small ubiquitinated peptides, remains unexplored. One member of the UCH family, UCH L1, is expressed in a number of malignancies suggesting that this DUB might be involved in oncogenic processes, and increased expression and activity of UCH L1 have been detected in EBV-immortalized cell lines. Here we present an analysis of genes regulated by UCH L1 shown by microarray profiles obtained from cells in which expression of the gene was inhibited by RNAi. Microarray data were verified with subsequent real-time PCR analysis. We found that inhibition of UCH L1 activates genes that control apoptosis, cell cycle arrest and at the same time suppresses expression of genes involved in proliferation and migration pathways. These findings are complemented by biological assays for apoptosis, cell cycle progression and migration that support the data obtained from microarray analysis, and suggest that the multi-functional molecule UCH L1 plays a role in regulating principal pathways involved in oncogenesis.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0006764