Previous studies have indicated that 6–30% of all newly synthesized proteins are rapidly degraded by the ubiquitin-proteasome system, however the relationship of ubiquitination to translation for these proteins has been unclear. We report that co-translational ubiquitination (CTU) is a robust process, with ~12–15% of nascent polypeptides being ubiquitinated in human cells. CTU products contained primarily K48-linked polyubiquitin chains, consistent with a proteasomal targeting function. While nascent chains have been shown previously to be ubiquitinated within stalled complexes (CTUS), the majority of nascent chain ubiquitination occurred within active translation complexes (CTUA). CTUA was increased in response to agents that induce protein misfolding, while CTUS was increased in response to agents that lead to translational errors or stalling. These results indicate that ubiquitination of nascent polypeptides occurs in two contexts, and define CTUA as a component of a quality control system that marks proteins for destruction while they are being synthesized.

The step by step assembly process from preribosome in the nucleus to translation-competent 60S ribosome subunit in the cytoplasm is revealed (also see Kemmler et al. in this issue).

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A typical pavement management system (PMS) should help a decision maker select the best maintenance program—that is, which maintenance treatment to use and where and when to apply it—so that maximal use is made of available resources. To provide decision support, a PMS needs a process for setting maintenance and rehabilitation (M&R) priorities. The quality of the prioritization directly influences the effectiveness of available resources, which in most cases is the primary goal of the decision maker. A network-level project selection procedure that uses an operations research optimization method was developed. An integer linear programming model was established to select a set of candidate projects from the highway network over a planning horizon of 5 years. In the model, constraints of available annual budgets and minimum requirements on pavement conditions were satisfied where state transition of each road section was formulated. Two optimization objectives—maximization of the total M&R effectiveness and minimization of the total M&R disturbance cost— were pursued over the planning horizon. A small network of 10 road sections was used as a pilot study for the established model. Pavement management functionalities at the network level are summarized, formulation of the integer linear programming model for the project selection problem is presented, differences in decision makers' value systems and the resulting different undominated solutions are discussed, and a sensitivity analysis of the annual budget constraint is conducted.

Newly synthesized proteins can be misfolded or damaged because of errors during synthesis or environmental insults (e.g., heat shock), placing a significant burden on protein quality control systems. In addition, numerous human diseases are associated with a deficiency in eliminating aberrant proteins or accumulation of aggregated proteins. Understanding the mechanisms of protein quality control and disposal pathways for misfolded proteins is therefore crucial for therapeutic intervention in these diseases. Quality control processes function at many points in the life cycle of proteins, and a subset act at the actual site of protein synthesis, the ribosome. Here we summarize recent advances in the role of the ubiquitin proteasome system in protein quality control during the process of translation.