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Cutting edge: proteasome involvement in the degradation of unassembled Ig light chains

T O'Hare1, G D Wiens, E A Whitcomb

  • 1Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|June 29, 1999
PubMed

Several studies on disposal of nonsecreted Ig L chains have identified the endoplasmic reticulum as the site of degradation. Here, we examine degradation of a nonsecreted Ig L chain, T15L, and an experimentally endoplasmic reticulum-retained secretion-competent L chain, D16L, in the absence of H chains. We demonstrate that 1) degradation is specifically impaired by the proteasome-specific inhibitors carboxybenzyl-leucyl-leucyl-leucine vinyl sulfone (Z-L3VS) and lactacystin, 2) L chain degradation occurs early in the biosynthetic pathway, and 3) degradation does not require vesicular transport. Our findings indicate that previous assertions of L chain disposal within the endoplasmic reticulum must be modified. To our knowledge, we provide the first direct evidence supporting a new paradigm for removal of nonsecreted Ig L chains via dislocation to cytosolic proteasomes.

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