Characterization of rapidly degraded polypeptides in mammalian cells reveals a novel layer of nascent protein quality control - PubMed (original) (raw)
. 2006 Jan 6;281(1):392-400.
doi: 10.1074/jbc.M509126200. Epub 2005 Nov 1.
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- PMID: 16263705
- DOI: 10.1074/jbc.M509126200
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Characterization of rapidly degraded polypeptides in mammalian cells reveals a novel layer of nascent protein quality control
Shu-Bing Qian et al. J Biol Chem. 2006.
Free article
Abstract
Approximately 30% of polypeptides synthesized by mammalian cells are degraded with a half-life of <10 min by proteasomes. These rapidly degraded polypeptides (RDPs) constitute the bulk of proteasome substrates and are the principal source of viral and self-peptide ligands for major histocompatibility complex class I molecules. Here we provide evidence that approximately 75% of RDPs are degraded by the standard ubiquitin 26 S proteasome system and that their degradation is regulated by modulating Hsc70 activity in cells. Surprisingly, the remaining approximately 25% of RDPs are degraded without ubiquitylation by 20 S proteasomes independently of 19 S regulators and in a manner that is largely unaffected by modulating Hsc70 activity. This latter pathway is utilized for generating an antigenic peptide from viral-defective ribosomal products. The dichotomy in the behavior of RDPs points to a novel quality control level for nascent proteins that is independent of the well established Hsc70-ubiquitin 26 S proteasome pathway.
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