Details

Autor(en) / Beteiligte

• Hughes, Eric A.
• Hammond, Craig
• Cresswell, Peter

Titel

Misfolded Major Histocompatibility Complex Class I Heavy Chains are Translocated into the Cytoplasm and Degraded by the Proteasome

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1997-03, Vol.94 (5), p.1896-1901

Ort / Verlag

United States: National Academy of Sciences of the United States of America

Erscheinungsjahr

1997

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• N-acetyl-L-leucyl-L-leucyl-L-norleucinal (LLnL), which reversibly inhibits the proteasome in addition to other proteases, and a more specific irreversible inhibitor of the proteasome, lactacystin, were found to cause the accumulation of major histocompatibility complex (MHC) class I heavy chains in the cytosol of the β 2-microglobulin-deficient cell line Daudi and the TAP-deficient cell line.174. These cell lines, which are severely impaired in their ability to fold MHC class I heavy chain, showed an accumulation of soluble class I heavy chains at different rates over a period of hours in the presence of LLnL. The accumulation of soluble class I heavy chains in the presence of either LLnL or lactacystin was easily revealed in Daudi and.174 but almost undetectable in a Daudi transfectant expressing β 2-microglobulin and in 45.1, the wild-type parent of.174. The soluble class I heavy chain was also found to be devoid of its N-linked glycan and to be located in the cytosol. When the gene for ICP47, a herpes simplex virus protein that blocks the translocation of peptides into the endoplasmic reticulum, was transfected into 45.1, a similar accumulation of soluble MHC class I heavy chain was detectable. These data suggest that in cells where the MHC class I molecule is unable to assemble properly, the misfolded heavy chain is removed from the endoplasmic reticulum to the cytosol, deglycosylated, and degraded by the proteasome.