Journal
PLOS ONE
Volume 6, Issue 1, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0014514
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Funding
- National High Technology Research and Development Program of China [2006AA02Z330, 2006AA02A301]
- Chinese Academy of Sciences [KSCX1-YW-R-74, KSCX1-YW-22]
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Deubiquitinating enzymes (DUBs) are important regulators of cell proliferation. Here we identified a functional deubiquitinating enzyme, ovarian tumor domain-containing 6B (OTUD-6B). Mutation of the conserved Cys residue abolished its deubiquitinating activity in vitro. Otud-6b expression was induced with cytokine stimulation in both mouse Ba/F3 cells and primary B lymphocytes followed a rapid decrease. This rapid decrease was partially facilitated by tristetraprolin (TTP) destabilization of Otud-6b mRNA through AU-rich motifs. Enforced expression of OTUD-6B in Ba/F3 cells could block cell proliferation by arresting cells in G1 phase. In addition, cyclin D2 level was down-regulated when OTUD-6B WT was overexpressed. Therefore, down-regulation of Otud-6b expression after prolonged cytokine stimulation may be required for cell proliferation in B lymphocytes.
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