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KMID : 0352819930090020079
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Kosin Medical Journal
1993 Volume.9 No. 2 p.79 ~ p.92
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Mechanism of endoplasmic reticulum retentionadn degradation of transmembrane proteins and T cell antigen receptor , chains.
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Abstract
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Right after synthesis inthe rough ER. secretory and cell surface expression proteins are initially modified in the lumen of the ER, followed by further modifications in the golgi and vesicular transport to their predestined place, e.g. cell
surface
or
secretion. In contrast, ER resident proteins, both ER lumenal and transmembrane proteins, escape from the vesicular transport by using specific retention signals. CD4, a cell surfacellular domains, a single transmembrane region, and a 38 amino
acid
olng
cytoplasmic region. The mutant of CD4, in which the cytoplasmic C-terminal 13 amino acids were truncated, was not expressed on the cell surface but was retained in the ER. The C-terminal amino acids (Lys-Lys-X-X) of this mutant may have the
sequence
information for ER retention and possibly all transmembrane proteins. This retention motif functions only in the presence of a transmembrane region. By contrast, the -Lys-Lys-Glu-Leu motif, which targets ER lumenal proteins, does not function in
the
presence of a transmembrane region. These results suggest that two distinct mechansisms are involved in ER retention or ER resident proteins.
The T cell antigen receptor-CD3(TCR/CD3) complex which is known to be composed of at least seven polypeptides is a key molecule in immune recognition and regulation. Cell surface expression of this complex (and degradation of excessively
synthesized TCR
chains) is strictly regulated in the ER. Both TCR and chains are rapidly degraded in the ER unless they are transported to the cell surface after formation of such big complex in the ER. In the present work, mechanism for Er degradation of TCR
chains is
proposexd.ER degradation of unassembled TCR chain is caused by exposure of hydrophobic transmembrane region to the polar enviroment of the Er lumen. Based on this observation, we hypothesize htat any misfolded or denatured proteins would be
subjected to
ER degradation by exposing their hydrophobic regions tothe degradation systems. This hypothesis can be supported by the observation ofTCR chain degradation in the ER.
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KEYWORD
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