Cutting edge: proteasome involvement in the degradation of unassembled Ig light chains.
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.
O'Hare
T
T
Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA.
Wiens
G D
GD
Whitcomb
E A
EA
Enns
C A
CA
Rittenberg
M B
MB
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003593:Cytoplasm / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D006056:Golgi Apparatus / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D008247:Lysosomes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009097:Multienzyme Complexes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D009101:Multiple Myeloma; D009194:Myeloma Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015853:Cysteine Proteinase Inhibitors; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D009097:Multienzyme Complexes; D009194:Myeloma Proteins; C043925:myeloma protein TEPC15; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex