Regulation of hematopoiesis by the K63-specific ubiquitin-conjugating enzyme Ubc13

The ubiquitin-conjugating enzyme Ubc13 mediates lysine-63-specific protein ubiquitination involved in signal transduction by immune receptors; however, the in vivo physiological functions of Ubc13 remain incompletely understood. Using Ubc13 conditional knockout mice, we show that somatic deletion of the Ubc13 gene causes severe loss of multi lineages of immune cells, which is associated with profound atrophy of the thymus and bone marrow, as well as lethality of the mice. Ubc13 has a cell-intrinsic function in mediating hematopoiesis and is essential for the survival and accumulation of hematopoietic stem cells in the bone marrow. Interestingly, loss of Ubc13 results in accumulation of beta-catenin and hyperexpression of Wnt target genes, a condition known to cause impaired hematopoiesis. These results establish Ubc13 as a crucial regulator of hematopoiesis and suggest a role for Ubc13 in the control of Wnt signaling in hematopoietic stem cells.