The small GTPase Rac1 is a novel binding partner of Bcl-2 and stabilizes its antiapoptotic activity

Abstract

The small GTPase Rac1 is involved in the activation of the reduced NAD phosphate oxidase complex resulting in superoxide production. We recently showed that Bcl-2 overexpression inhibited apoptosis in leukemia cells by creating a pro-oxidant intracellular milieu, and that inhibiting intracellular superoxide production sensitized Bcl-2-overexpressing cells to apoptotic stimuli. We report here that silencing and functional inhibition of Rac1 block Bcl-2-mediated increase in intracellular superox-

RacGAP1 Is a Novel Downstream Effector of E2F7-Dependent Resistance to Doxorubicin and Is Prognostic for Overall Survival in Squamous Cell Carcinoma

“…These data suggest that the resistance to doxorubicin correlates with the GTP-loaded "active" state of Rac1. This conclusion is supported by a previous study showing that the antiapoptotic protein, Bcl-2, interacts with Rac1 to protect tumor cells from the cytotoxic actions of etoposide and daunorubicin (48). Moreover, our conclusion is also consistent with a previous report suggesting that Rac1 was a potential therapeutic target in chemoradioresistant HNSCC (49).…”

Tiam1/Rac1 signals contribute to the proliferation and chemoresistance, but not motility, of chronic lymphocytic leukemia cells

“…First, Rac1 was shown to interact with Bcl-2 and to stabilize its antiapoptotic activity in lymphoma. 56 Concurrent exposure to NSC-23766 increased the apoptotic effect of the Bcl-2 inhibitor and BH3 mimetic ABT-737 in leukemia cells. 57 Bcl-2 overexpression is a hallmark of CLL 58 .…”

Mitochondrial Rac1 GTPase Import and Electron Transfer from Cytochrome c Are Required for Pulmonary Fibrosis

“…Recent evidence has shown that Rac1 interacts with Bcl-2 in the mitochondria of lymphocytes, but Bcl-2, rather than Rac1, was coupled to mitochondrial ROS generation (32). In contrast, the ability of Rac1 to translocate into the mitochondria and accept electrons represents a new mechanistic insight into how Rac1 can facilitate the generation of H 2 O 2 by partial reduction of O 2 in macrophages.…”