平特五不中

The endoplasmic reticulum (ER) is the site of synthesis of antibodies that are either destined to be expressed on the cell surface or secreted.聽 These proteins enter the ER through a protein channel as extended polypeptide chains and interact with a variety of molecular chaperones and folding enzymes that help them achieve their proper mature tertiary and quaternary structures, which in their simplest form requires the assembly of two heavy and two light chains.聽 If successful, the antibody leaves the ER to travel to its appropriate destination outside the cell.聽 If however, the nascent heavy or light chain fails to fold or assemble properly, it must be identified and targeted for retrotranslocation to the cytosol for degradation by the 26S proteasome, which involves some of the same molecular chaperones.聽 There are a number of unresolved issues concerning how the ER quality control machinery can distinguish between proteins that have not yet folded and those that cannot fold, as it is expected that both types of proteins would have very similar features.聽 In addition, the folding of many nascent proteins is dependent on the oxidizing environment of the ER, whereas the degradation of misfolded proteins often requires that those portions of the protein that have folded be reduced to allow them to pass through the retrotranslocon.聽 Finally, any protein that is synthesized in the ER has the potential to misfold, arguing that the ubiquitin/proteasome system must be poised to recognize every type of secretory pathway produced in that cell.聽 How such broad specificity is executed remains unclear. Progress from our lab on these issues and how this contributes to understanding how the ER orchestrates seemingly opposing functions will be presented.