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, 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.
Bheda
Anjali
A
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.
Shackelford
Julia
J
Pagano
Joseph S
JS
D017209:Apoptosis; D001483:Base Sequence; D002453:Cell Cycle; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D017931:DNA Primers; D005786:Gene Expression Regulation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043222:Ubiquitin Thiolesterase / Q000502:physiology*
D017931:DNA Primers; D043222:Ubiquitin Thiolesterase
Lung Cancer. 2003 Oct;42(1):9-21
14512183
Proc Natl Acad Sci U S A. 1982 Nov;79(21):6651-5
6292911
Anticancer Res. 2008 Sep-Oct;28(5A):2697-700
19035297
Clin Cancer Res. 2007 Jan 1;13(1):27-37
17200335
Mod Pathol. 2003 Oct;16(10):963-9
14559978
Jpn J Clin Oncol. 2001 Nov;31(11):532-5
11773260
J Cell Mol Med. 2009 Aug;13(8B):1666-1678
20187292
Neurochem Int. 2007 Jul-Sep;51(2-4):105-11
17586089
Brain Res Mol Brain Res. 2004 Jul 5;126(1):88-97
15207921
PLoS One. 2009 Jun 18;4(6):e5955
19536331
J Cell Biochem. 2007 Dec 15;102(6):1400-4
17979151
Int J Cancer. 2008 Jul 1;123(1):32-40
18398830
Hum Mol Genet. 2003 Aug 15;12(16):1945-58
12913066
Semin Cancer Biol. 2002 Jun;12(3):187-95
12083849
Anticancer Res. 2004 Nov-Dec;24(6):3731-4
15736404
Hepatogastroenterology. 2003 Sep-Oct;50(53):1278-80
14571718
Clin Cancer Res. 2006 Mar 15;12(6):1820-7
16551867
Neurosci Lett. 2006 Oct 23;407(2):124-6
16978776
Cell Cycle. 2004 Mar;3(3):343-8
14726710
Oncogene. 1999 May 13;18(19):2988-96
10378694
Oncogene. 2002 May 2;21(19):3003-10
12082530
Science. 1989 Nov 3;246(4930):670-3
2530630
Cancer Sci. 2006 Jun;97(6):523-9
16734731
Eur J Cancer. 2004 Mar;40(4):614-8
14962731
Enzyme Protein. 1996;49(5-6):262-72
9252784
J Proteome Res. 2009 Aug;8(8):3977-86
19545154
Mol Carcinog. 2006 Apr;45(4):260-9
16402389
Oncogene. 2009 Jan 8;28(1):117-27
18820707
Mol Cell Biochem. 2008 Nov;318(1-2):109-15
18622688
Cancer Biol Ther. 2002 Jul-Aug;1(4):337-41
12432242
Apoptosis. 2006 Jun;11(6):1049-59
16544100
J Virol. 1999 Jun;73(6):4678-88
10233927
Cell. 2002 Oct 18;111(2):209-18
12408865
Curr Mol Med. 2003 Nov;3(7):659-71
14601640
Drug Resist Updat. 2007 Feb-Apr;10(1-2):13-29
17303468
J Neurochem. 1983 Jun;40(6):1542-7
6343558
Crit Rev Oncog. 2000;11(1):63-76
10795627
Prostate. 2007 Dec 1;67(16):1761-9
17929277
Nature. 2004 Nov 18;432(7015):298-306
15549091
FASEB J. 1997 Dec;11(14):1245-56
9409543
Clin Cancer Res. 2000 Dec;6(12):4764-7
11156232