DUB-2A, a new member of the DUB subfamily of hematopoietic deubiquitinating enzymes.
Protein ubiquitination is an important regulator of cytokine-activated signal transduction pathways and hematopoietic cell growth. Protein ubiquitination is controlled by the coordinate action of ubiquitin-conjugating enzymes and deubiquitinating enzymes. Recently a novel family of genes encoding growth-regulatory deubiquitinating enzymes (DUB-1 and DUB-2) has been identified. DUBs are immediate-early genes and are induced rapidly and transiently in response to cytokine stimuli. By means of polymerase chain reaction amplification with degenerate primers for the DUB-2 complementary DNA, 3 murine bacterial artificial chromosome (BAC) clones that contain DUB gene sequences were isolated. One BAC contained a novel DUB gene (DUB-2A) with extensive homology to DUB-2. Like DUB-1 and DUB-2, the DUB-2A gene consists of 2 exons. The predicted DUB-2A protein is highly related to other DUBs throughout the primary amino acid sequence, with a hypervariable region at its C-terminus. In vitro, DUB-2A had functional deubiquitinating activity; mutation of its conserved amino acid residues abolished this activity. The 5' flanking sequence of the DUB-2A gene has a hematopoietic-specific functional enhancer sequence. It is proposed that there are at least 3 members of the DUB subfamily (DUB-1, DUB-2, and DUB-2A) and that different hematopoietic cytokines induce specific DUB genes, thereby initiating a cytokine-specific growth response. (Blood. 2001;98:636-642)
Baek
K H
KH
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Mondoux
M A
MA
Jaster
R
R
Fire-Levin
E
E
D'Andrea
A D
AD
D000818:Animals; D001483:Base Sequence; D020134:Catalytic Domain; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003001:Cloning, Molecular; D016207:Cytokines / Q000494:pharmacology; D018076:DNA, Complementary; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology; D004742:Enhancer Elements, Genetic / Q000187:drug effects; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D014452:Ubiquitins / Q000378:metabolism
D016207:Cytokines; D018076:DNA, Complementary; D006133:Growth Substances; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014452:Ubiquitins; C103857:Dub2 protein, mouse; C433930:Dub2a protein, mouse; D010450:Endopeptidases