Mechanisms for the temporal regulation of substrate ubiquitination by the anaphase-promoting complex/cyclosome

The anaphase-promoting complex/cyclosome (APC/C) is a multi-subunit, multifunctional ubiquitin ligase that controls the temporal degradation of numerous cell cycle regulatory proteins to direct the unidirectional cell cycle phases. Several different mechanisms contribute to ensure the correct order of substrate modification by the APC/C complex. Recent advances in biochemical, biophysical and structural studies of APC/C have provided a deep mechanistic insight into the working of this complex ubiquitin ligase. This complex displays remarkable conformational flexibility in response to various binding partners and post-translational modifications, which together regulate substrate selection and catalysis of APC/C. Apart from this, various features and modifications of the substrates also influence their recognition and affinity to APC/C complex. Ultimately, temporal degradation of substrates depends on the kind of ubiquitin modification received, the processivity of APC/C, and other extrinsic mechanisms. This review discusses our current understanding of various intrinsic and extrinsic mechanisms responsible for ‘substrate ordering’ by the APC/C complex.

Information recovery following a retrospective cue decreases with time

Working memory (WM) performance can be enhanced by an informative cue presented during storage. This effect, termed a retrocue benefit, can be used to explore how observers prioritize information stored in WM to guide behavior. Recent studies have demonstrated that neural representations of task-relevant memoranda are strengthened following the appearance of a retrocue, suggesting that participants can consult alternative information stores to supplement active memory traces. Here, we sought to better understand the nature of these memory store(s) by asking whether they are subject to the same temporal degradation seen in active memory representations. We reconstructed and quantified representations of remembered positions from alpha-band EEG activity recorded while participants performed a retrospectively cued spatial WM task, and varied the temporal interval separating the encoding display and retrocue. Although we observed a partial recovery of location information in all cue conditions, the magnitude of recovery was linearly and inversely related to the timing of the retrocue. This suggests that participants’ ability to supplement active memory representations with information from additional memory stores is not static: the information maintained in these stores may be subject to temporal degredation, or the stores themselves may become more difficult to access with time.