Abstract
Cell can integrate the caspase family and mammalian target of rapamycin (mTOR) signaling in response to cellular stress triggered by environment. It is necessary here to elucidate the direct response and interaction mechanism between the two signaling pathways in regulating cell survival and determining cell fate under cellular stress. Members of the caspase family are crucial regulators of inflammation, endoplasmic reticulum stress response and apoptosis. mTOR signaling is known to mediate cell growth, nutrition and metabolism. For instance, over-nutrition can cause the hyperactivation of mTOR signaling, which is associated with diabetes. Nutrition deprivation can inhibit mTOR signaling via SH3 domain-binding protein 4. It is striking that Ras GTPase-activating protein 1 is found to mediate cell survival in a caspase-dependent manner against increasing cellular stress, which describes a new model of apoptosis. The components of mTOR signaling-raptor can be cleaved by caspases to control cell growth. In addition, mTOR is identified to coordinate the defense process of the immune system by suppressing the vitality of caspase-1 or regulating other interferon regulatory factors. The present review discusses the roles of the caspase family or mTOR pathway against cellular stress and generalizes their interplay mechanism in cell fate determination.
Highlights
The optimal growth of cell is closely connected to the stress response
We focus on the cross talk of the two pathways in the determination of cell life and death
Other research has demonstrated that in breast epithelial cells with ERBB2 oncogene mutation, hyperactivation of the PKR-like ER kinase (PERK)/ATF4/C/EBP homologous protein (CHOP) pathway leads to the upregulation of pro-apoptotic cell surface receptor TNF related apoptosis inducing ligand (TRAIL)-receptor 2 expression while undergoing endoplasmic reticulum (ER) stress, following a formation of a death-inducing signaling complex (DISC) complex composed of TRAIL-receptor 2, Fas-associating protein with a novel death domain and pro-caspase-8, resulting in the activation of caspase-8 in response to the ER stress-induced apoptosis [58]
Summary
It is necessary to integrate the pro-growth signaling and stress response pathways to maintain the balance of growth and death. Once this balance is destroyed, malignant proliferation or cell death will occur and the organism will develop diseases such as tumors. Caspase family members are powerful function proteins that respond to cellular stress including cell death signals, inflammation and ER stress [2,3,4]. Caspases-mediated apoptosis is a kind of suicide protective measure initiated by gene regulation, which aims at eliminating redundant, damaged or effete cells under stress [5]. Existing research has identified the critical regulation mechanism between mTOR signaling and the caspase family [8,9]. We focus on the cross talk of the two pathways in the determination of cell life and death
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