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Subsequently, conformational changes in TR-I allow the phosphorylation of signaling molecules called receptor-regulated (R)-SMAD (i.e., SMAD 2,3)

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The cellular consequences of IF/aggregate proportion changes are not clear, and the question as to whether these structures correspond to an aggresome uncoating step 54,55 prior to content degradation via autophagy remains to be addressed

Covalent/irreversible inhibitors target the redox/catalytic apparatus of TGR with almost no recognition elements that give affinity and selectivity for TGR over off-targets and the cellular redox apparatus resulting in undesirable cross-reactions and low specificity in vivo 25