000267421 001__ 267421
000267421 005__ 20190625154534.0
000267421 022__ $$a1040-9238
000267421 022__ $$a1549-7798
000267421 02470 $$2isi$$a000470511000001
000267421 0247_ $$a10.1080/10409238.2019.1610351$$2doi
000267421 037__ $$aARTICLE
000267421 245__ $$aProteasomal and lysosomal clearance of faulty secretory proteins: ER-associated degradation (ERAD) and ER-to-lysosome-associated degradation (ERLAD) pathways
000267421 269__ $$a2019-05-03
000267421 260__ $$c2019-05-03
000267421 336__ $$aReviews
000267421 520__ $$aAbout 40% of the eukaryotic cell's proteins are inserted co- or post-translationally in the endoplasmic reticulum (ER), where they attain the native structure under the assistance of resident molecular chaperones and folding enzymes. Subsequently, these proteins are secreted from cells or are transported to their sites of function at the plasma membrane or in organelles of the secretory and endocytic compartments. Polypeptides that are not delivered within the ER (mis-localized proteins, MLPs) are rapidly destroyed by cytosolic proteasomes, with intervention of the membrane protease ZMPSTE24 if they remained trapped in the SEC61 translocation machinery. Proteins that enter the ER, but fail to attain the native structure are rapidly degraded to prevent toxic accumulation of aberrant gene products. The ER does not contain degradative devices and the majority of misfolded proteins generated in this biosynthetic compartment are dislocated across the membrane for degradation by cytosolic 26S proteasomes by mechanisms and pathways collectively defined as ER-associated degradation (ERAD). Proteins that do not engage ERAD factors, that enter aggregates or polymers, are too large, display chimico/physical features that prevent dislocation across the ER membrane (ERAD-resistant misfolded proteins) are delivered to endo-lysosome for clearance, by mechanisms and pathways collectively defined as ER-to-lysosomes-associated degradation (ERLAD). Emerging evidences lead us to propose ERLAD as an umbrella term that includes the autophagic and non-autophagic pathways activated and engaged by ERAD-resistant misfolded proteins generated in the ER for delivery to degradative endo-lysosomes.
000267421 650__ $$aBiochemistry & Molecular Biology
000267421 650__ $$aBiochemistry & Molecular Biology
000267421 6531_ $$aautophagy
000267421 6531_ $$aendo-lysosomes
000267421 6531_ $$aendoplasmic reticulum (er)
000267421 6531_ $$aer-associated degradation (erad)
000267421 6531_ $$aer-phagy and er-phagy receptors
000267421 6531_ $$aer-to-lysosome-associated degradation (erlad)
000267421 6531_ $$aprotein folding and quality control
000267421 6531_ $$arecover-phagy
000267421 6531_ $$areticulum-associated-degradation
000267421 6531_ $$acytosolic quality-control
000267421 6531_ $$aubiquitin ligase complex
000267421 6531_ $$aendoplasmic-reticulum
000267421 6531_ $$aalpha-1-antitrypsin deficiency
000267421 6531_ $$amisfolded glycoproteins
000267421 6531_ $$alc3-associated phagocytosis
000267421 6531_ $$amutant alpha-1-antitrypsin
000267421 6531_ $$aintracellular degradation
000267421 6531_ $$aalpha(1)-antitrypsin z
000267421 700__ $$aFregno, Ilaria
000267421 700__ $$g189940$$aMolinari, Maurizio
000267421 773__ $$j54$$q153-163$$k2$$tCritical Reviews In Biochemistry And Molecular Biology
000267421 8560_ $$fbeatrice.marselli@epfl.ch
000267421 909C0 $$xU11270$$pGHI$$0252451
000267421 909CO $$preview$$particle$$ooai:infoscience.epfl.ch:267421$$pSV
000267421 961__ $$abeatrice.marselli@epfl.ch
000267421 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000267421 981__ $$aoverwrite
000267421 980__ $$aARTICLE