Proteomics

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Hepatic p62, a major autophagic receptor in CYP4A ALD


ABSTRACT: In cell DSS crosslinking of HEK293 cells expressing His-tagged CYP4A11 and HA-tagged p62. Cells were treated with DSS, lysed, and enriched by Ni-NTA affinity chromatography. The eluate was separated by SDS-PAGE and the CYP-p62 crosslinked band identified by multi-channel western blot visualization. The crosslinked band was excised and in gel digested. Crosslinked peptides were analyzed on an Orbtrap Exploris 480 with a FAIMS source and running a 0.75 um x 50 cm c18 column with a 4-hour separation. The sample was injected twice using two different sets of compensation voltages: S20240820-04.raw: -45, -60, -70 V. S20240820-05: -40, -50, -65C.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Maria Almira Correia  

PROVIDER: MSV000096827 | MassIVE | Fri Jan 10 15:46:00 GMT 2025

REPOSITORIES: MassIVE

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Publications

Liver CYP4A autophagic-lysosomal degradation (ALD): A major role for the autophagic receptor SQSTM1/p62 through an uncommon target interaction site.

He Liang L   Kwon Doyoung D   Trnka Michael J MJ   Liu Yi Y   Yang Jade J   Li Kathy K   Totah Rheem A RA   Johnson Eric F EF   Burlingame A L AL   Correia Maria Almira MA  

bioRxiv : the preprint server for biology 20241014


The hepatic P450 hemoproteins CYPs 4A are typical N-terminally anchored Type I endoplasmic reticulum (ER)-proteins, that are inducible by hypolipidemic drugs and other "peroxisome proliferators". They are engaged in the ω-/ω-1-oxidation of various fatty acids including arachidonic acid, prostaglandins and leukotrienes and in the biotransformation of some therapeutic drugs. Herein we report that of the mammalian liver CYPs 4A, human CYP4A11 and mouse Cyp4a12a are preferential targets of the ER-ly  ...[more]

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