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The signaling cascades initiated upon activation of oncogenic Ras and other small GTPases remain to be fully understood, especially in the context of Ras-mediated resistance to DNA-damage inducers. For example, it has been shown that, in response to Ras activation, cells display enhanced resistance to DNA-damage agents. The mechanism(s) underlying this paradoxical phenomenon of Ras-induced resistance have been unclear. Recently, we have identified a novel GTPase effector, termed mRasGEF (RasGEF), which specifically binds and regulates Ras. Using a mammalian two-hybrid system, we show here that mRasGEF functions as a dual Ras GTPase effector, interacting with not only Ras but also rhoA. Indeed, rhoA- but not Ras-mediated cell transformation is stimulated by mRasGEF. Furthermore, mRasGEF is rapidly recruited to mitochondria upon Ras activation. Overexpression of either constitutively active or dominant negative mRasGEF leads to altered DNA damage response and enhanced radioresistance in mammalian cells. Collectively, these findings suggest that mRasGEF may function as a point of convergence of Ras and rhoA signaling in the regulation of DNA damage response.The role of damage control laparotomy in the protection of patients in the physiologic and psychological aftermath of oncologic trauma.
The prolonged trauma of oncologic injury is increasingly recognized to cause significant damage to mental health. A particular concern is how to effectively convey the severity of a cancer diagnosis to the patient and how to protect the patient from re-traumatization. These issues have led to the development of several guidelines for the structure and process of the transition of the patient from the trauma of the initial oncologic insult
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