000002211 001__ 2211 000002211 005__ 20260505132242.0 000002211 0247_ $$2DOI$$a10.6083/M44Q7S82 000002211 037__ $$aETD 000002211 245__ $$aMechanism of cftr dislocation during endoplasmic reticulum-associated degradation 000002211 260__ $$bOregon Health and Science University 000002211 269__ $$a2006 000002211 336__ $$aDissertation 000002211 502__ $$bPh.D. 000002211 502__ $$gCell & Developmental Biology (sunsetting) 000002211 520__ $$bCystic fibrosis is caused by mutations in CFTR, a protein largely degraded by the proteasome, with the common ΔF508 mutation undergoing near-complete degradation. To identify components of CFTR degradation, membrane and cytosolic factors were examined. While inactivation of membrane proteins had no effect, depletion of cytosolic factors reduced degradation. Proteomic analysis identified the AAA-ATPase p97 as a key factor. p97 depletion decreased CFTR degradation efficiency and selectively impaired degradation of stable transmembrane domains, indicating that p97 enhances proteasomal dislocation and degradation during ER-associated degradation. 000002211 540__ $$fCC BY 000002211 542__ $$fIn copyright - single owner 000002211 650__ $$aGenetics$$019472 000002211 650__ $$aCystic Fibrosis Transmembrane Conductance Regulator$$031275 000002211 650__ $$aCystic Fibrosis$$017315 000002211 650__ $$aEndoplasmic Reticulum$$018433 000002211 650__ $$aPhysiology$$024123 000002211 650__ $$aProteasome Endopeptidase Complex$$035896 000002211 650__ $$aUbiquitin$$033233 000002211 650__ $$aProteasome Endopeptidase Complex$$035896 000002211 650__ $$aEndoplasmic Reticulum-Associated Degradation$$039795 000002211 691__ $$aSchool of Medicine$$041369 000002211 692__ $$aDepartment of Cell, Developmental and Cancer Biology$$041399 000002211 7001_ $$aCarlson, Eric$$uOregon Health and Science University$$041354 000002211 8564_ $$9fb0d7060-1e9c-4e30-a0dd-55032ad7f9f9$$s3773377$$uhttps://digitalcollections.ohsu.edu/record/2211/files/2940_etd.pdf$$ePublic$$2fe0031dea70f099756d05d1d8bdd6497$$31 000002211 901__ $$a<p>These documents are archival records. They are retained for historical reference only. </p><p><b>Need an accessible version? Use the ‘Get Accessible Copy’ link above.</b></p> 000002211 905__ $$a/rest/prod/1j/92/g7/60/1j92g760n 000002211 909CO $$ooai:digitalcollections.ohsu.edu:2211$$pstudent-work 000002211 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument 000002211 980__ $$aTheses and Dissertations