Classic paper: Presentation from ER proteins

I have a very sporadic and idiosyncratic series in which I talk about “classic papers”, and in my idiosyncratic series Vic Engelhard’s paper on tyrosinase processing counts as a classic paper. It was one of the early indications that proteins in the ER must be degraded in the cytosol, and as such it’s one of a number of ways that antigen presentation has helped fundamental understanding of cell biology; but I think it hasn’t received as much recognition as it could have.
But perhaps I should begin at the beginning.
Proteolysis is a normal part of cell function. Proteins that are damaged, misfolded, or mis-translated, as well as proteins that have simply reached the end of their useful life, are degraded and converted to amino acids that can be recycled into new proteins. In the early- to mid-1990s, there were three general systems that were known to degrade proteins, depending on which subcellular compartment they were in:
In the cytosol and nucleus, proteins are predominately degraded by proteasomes.
Proteins taken up from the exterior of the cell can be degraded in acidic lysosomes
Mitochondrial proteins are degraded by a number of proteases within the mitochondrion1
That leaves an obvious gap. What happens to proteins that are in the endoplasmic reticulum (ER)? This is particularly relevant because the ER is a ferociously active site of protein synthesis, folding, and assembly; when any of those steps goes awry, the protein is supposed to be degraded, a process known as “quality control”. It was clear in the 1980s that proteins that failed quality control in the ER were degraded; in human cells, a well-known example was the cystic fibrosis transmembrane conductance regulator (CFTR), which folds inefficiently and is rapidly degraded2. But it was not clear where the degradation happened (in the ER? The cytosol? Somewhere else?), and what proteases were responsible.
At first it was believed that “what happens in the ER stays in the ER” — ER proteins were degraded in the ER, by ill-defined proteases in that compartment. But I don’t think there was much enthusiasm for that belief, and basically, the field was a mess, as you can see from this introductory paragraph from the time:3
Other membrane proteins are also known to be degraded at the ER, but the process is poorly understood, and the responsible enzymes have not been identified. For example, some of these proteolytic events are ATP dependent, but some are not; some occur within the lumen while others take place on the cytoplasmic side; some exhibit inhibitor sensitivities characteristic of serine proteases, whereas others do not.