Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan.

Small-molecule inhibitors of indoleamine 2,3-dioxygenase (IDO) are currently being translated to clinic for evaluation as cancer therapeutics. One issue related to trials of the clinical lead inhibitor, D-1-methyl-tryptophan (D-1MT), concerns the extent of its biochemical specificity for IDO. Here, we report the discovery of a novel IDO-related tryptophan catabolic enzyme termed IDO2 that is preferentially inhibited by D-1MT.

RhoB facilitates c-Myc turnover by supporting efficient nuclear accumulation of GSK-3.

The small GTPase RhoB suppresses cancer in part by limiting cell proliferation. However, the mechanisms it uses to achieve this are poorly understood. Recent studies link RhoB to trafficking of Akt, which through its regulation of glycogen synthase kinase-3 (GSK-3) has an important role in controlling the stability of the c-Myc oncoprotein.

Genetic response to DNA damage: proapoptotic targets of RhoB include modules for p53 response and susceptibility to Alzheimer's disease.

Knockout mouse studies indicate that the small GTPase RhoB is critical for apoptosis triggered by genotoxic stress in transformed mouse cells. However, the mechanisms used by RhoB to sensitize cells to cell death are obscure. To gain insight into this question, we compared the genetic response of cells with different rhoB genotypes to the DNA damaging anticancer drug doxorubicin (DOX).