Influence of SHIP on the NK repertoire and allogeneic bone marrow transplantation.

Natural killer cell (NK) receptors for major histocompatibility complex (MHC) class I influence engraftment and graft-versus-tumor effects after allogeneic bone marrow transplantation. We find that SH2-containing inositol phosphatase (SHIP) influences the repertoire of NK receptors. In adult SHIP-/- mice, the NK compartment is dominated by cells that express two inhibitory receptors capable of binding either self or allogeneic MHC ligands.

Identification of novel E2F1-regulated genes by microarray.

The E2F pathway has been proposed to regulate genes involved in the transition from quiescence into DNA synthesis. However, this hypothesis has not been rigorously tested on a genomic scale. Toward this end, we have infected quiescent mouse fibroblasts, which do not express E2F1, with an E2F1-expressing adenovirus and examined the expression of more than 6000 genes using high-density microarrays.

Direct repression of the Mcl-1 promoter by E2F1.

E2F1 induces apoptosis via both p53-dependent and p53-independent mechanisms. The direct targets in the p53-independent pathway remain enigmatic; however, the induction of this pathway does not require the transactivation domain of E2F1. Using cells that are defective in p53 activation, we show that E2F1 potently represses the expression of Mcl-1--an anti-apoptotic Bcl-2 family member whose depletion results in apoptosis.