Bone cancer pain (BCP), as a common type of cancer pain, is a specific pain state that differs from inflammatory pain and neuropathic pain (Gadepalli et al., 2021). BCP brings a series of adverse effects, including nausea and vomiting, loss of appetite, anxiety, depression, fear and helplessness, which make the patients suffer (Sung et al., 2021). With advances in medical technology, most patients with malignancies have significantly longer survival (Sung et al., 2021). However, the bone disease and pain associated with metastatic cancer has yet to be addressed. The development of new therapeutic approaches and drug targets for BCP is, therefore, particularly urgent.Mas-related G protein-coupled receptor C (MrgC) is a member of the Mrg receptor family that are expressed in small-diameter primary sensory neurons. The activation of MrgC can inhibit a variety of pains including inflammatory pain, neuropathic pain and BCP (He et al., 2014;Jiang et al., 2013;Sun, Zhang, et al., 2016). Our previous studies have shown that MrgC plays an important role in the development of BCP, and can inhibit Ca2+ inward
BACKGROUND
Ubiquitin-mediated Mas-related G protein-coupled receptor C (MrgC) degradation contributes to development of agonist resistance. It has been shown that inhibition of ubiquitin-activating enzymes reduces the ubiquitination of MrgC. In this study we investigated the ubiquitin degradation pathway and ubiquitin chain type of MrgC.
METHODS
The degradation pathway of MrgC was studied by treating N2a cells with autophagy lysosome inhibitor and proteasome inhibitor. N2a cells were transfected with mutant ubiquitin plasmids to study the ubiquitin chain type of MrgC.
RESULTS
Autophagy lysosome inhibitors can inhibit the degradation of MrgC. Intracellular MrgC co-localized with lysosomes. MrgC proteins can link multiple types of ubiquitin chains.
CONCLUSION
Complex topology of ubiquitin chains mediates lysosomal degradation of MrgC proteins. Inhibition of ubiquitination degradation of MrgC may avoid agonist resistance of MrgC, maintaining its biological activity.
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