DUB-3, a cytokine-inducible deubiquitinating enzyme that blocks proliferation.
Previous studies have identified the DUB family of cytokine-regulated murine deubiquitinating enzymes, which play a role in the control of cell proliferation and survival. Through data base analyses and cloning, we have identified a human cDNA (DUB-3) that shows significant homology to the known murine DUB family members. Northern blotting has shown expression of this gene in a number of tissues including brain, liver, and muscle, with two transcripts being apparent (1.6 and 1.7 kb). In addition, expression was observed in cell lines including those derived from a number of hematopoietic tumors such as the Burkitt's lymphoma cell line RAJI. We have also demonstrated that DUB-3, which was shown to be an active deubiquitinating enzyme, is induced in response to interleukin-4 and interleukin-6 stimulation. Finally, we have demonstrated that constitutive expression of DUB-3 blocks proliferation and can initiate apoptosis in both IL-3-dependent Ba/F3 cells and NIH3T3 fibroblasts. These findings suggest that human DUB-3, like the murine DUB family members, is transiently induced in response to cytokines and can, when constitutively expressed, block growth factor-dependent proliferation.
Burrows
James F
JF
Department of Microbiology and Immunology, Queen's University, Belfast, Northern Ireland.
McGrattan
Michael J
MJ
Rascle
Anne
A
Humbert
Martine
M
Baek
Kwang-Hyun
KH
Johnston
James A
JA
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D025801:Ubiquitin / Q000378:metabolism*
D016207:Cytokines; D012333:RNA, Messenger; D025801:Ubiquitin; D010450:Endopeptidases; C484854:USP17L2 protein, human