Abstract：
:The 26S proteasome is the primary protease responsible for degrading misfolded membrane proteins in the endoplasmic reticulum. Here we examine the specific role of beta subunit function on polypeptide cleavage and membrane release of CFTR, a prototypical ER-associated degradation substrate with 12 transmembrane segments. In the presence of ATP, cytosol and fully active proteasomes, CFTR was rapidly degraded and released into the cytosol solely in the form of trichloroacetic acid (TCA)-soluble peptide fragments. Inhibition of proteasome beta subunits markedly decreased CFTR degradation but surprisingly, had relatively minor effects on membrane extraction and release. As a result, large TCA-insoluble degradation intermediates derived from multiple CFTR domains accumulated in the cytosol where they remained stably bound to inhibited proteasomes. Production of TCA-insoluble fragments varied for different proteasome inhibitors and correlated inversely with the cumulative proteolytic activities of beta1, beta2 and beta5 subunits. By contrast, ATPase inhibition decreased CFTR release but had no effect on the TCA solubility of the released fragments. Our results indicate that the physiologic balance between membrane extraction and peptide cleavage is maintained by excess proteolytic capacity of the 20S subunit. Active site inhibitors reduce this capacity, uncouple ATPase and peptidase activities, and generate cytosolic degradation intermediates by allowing the rate of unfolding to exceed the rate of polypeptide cleavage.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Oberdorf J,Carlson EJ,Skach WRdoi
10.1242/jcs.02732keywords:
subject
Has Abstractpub_date
2006-01-15 00:00:00pages
303-13issue
Pt 2eissn
0021-9533issn
1477-9137pii
jcs.02732journal_volume
119pub_type
杂志文章abstract：:We have investigated the role in macrophage lysosomal enzyme release of arachidonate metabolites, extracellular divalent cations and cyclic AMP (cAMP) which modulate secretion in other cell types. Lysosomal enzyme secretion induced by zymosan was accompanied by release of malondialdehyde (MDA), which is derived from a...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1980-08-01 00:00:00
abstract：:Double minutes (DMs) seen in a substantial fraction of human tumors are the cytogenetic manifestation of gene amplification which renders the tumor cells advantageous for growth and survival. DMs are acentric and atelomeric chromatin composed of circular DNA. In this study, we found they showed a remarkable relocation...
journal_title：Journal of cell science
pub_type： 杂志文章
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更新日期：1998-11-01 00:00:00
abstract：:When Swiss 3T3 cells are treated with colcemid for 60 min (0.5-2 micrograms/ml), although the cytoplasmic network of microtubules is considerably reduced, a significant but variable number of microtubules remain. These residual microtubules appear to converge on a single, usually ciliated, organizing centre. In contra...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
abstract：:The monoclonal antibody Bx63 recognizes a centrosomal antigen of Drosophila melanogaster by indirect immunofluorescence and identifies two proteins, with apparent molecular weights of 185 x 10(3) and 66 x 10(3), on Western blots. We have used this antibody to isolate five clones (lambda cs1, -2, -3, -4 and lambda j63)...
journal_title：Journal of cell science
pub_type： 杂志文章
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更新日期：1988-04-01 00:00:00
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journal_title：Journal of cell science
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更新日期：2010-12-15 00:00:00
abstract：:The morphogenesis-related NDR kinase (MOR) pathway regulates morphogenesis in fungi. In spite of the high conservation of its components, impairing their functions results in highly divergent cellular responses depending on the fungal species. The reasons for such differences are unclear. Here we propose that the spec...
journal_title：Journal of cell science
pub_type： 杂志文章
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更新日期：2012-10-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
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journal_title：Journal of cell science
pub_type： 杂志文章
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更新日期：1991-06-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2003-04-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
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更新日期：1999-12-01 00:00:00
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journal_title：Journal of cell science
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更新日期：2005-01-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1980-10-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.059196
更新日期：2009-11-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1997-12-01 00:00:00
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pub_type： 杂志文章
doi：10.1242/jcs.040162
更新日期：2009-07-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1980-04-01 00:00:00
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journal_title：Journal of cell science
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journal_title：Journal of cell science
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doi：
更新日期：1985-08-01 00:00:00
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更新日期：1994-12-01 00:00:00
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更新日期：2019-12-02 00:00:00
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journal_title：Journal of cell science
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journal_title：Journal of cell science
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更新日期：1995-03-01 00:00:00
