PMID- 30821613
OWN - NLM
STAT- MEDLINE
DCOM- 20200706
LR  - 20200706
IS  - 1554-8635 (Electronic)
IS  - 1554-8627 (Print)
IS  - 1554-8627 (Linking)
VI  - 15
IP  - 9
DP  - 2019 Sep
TI  - Targetome analysis of chaperone-mediated autophagy in cancer cells.
PG  - 1558-1571
LID - 10.1080/15548627.2019.1586255 [doi]
AB  - Chaperone-mediated autophagy (CMA) is a lysosomal degradation pathway of select 
      soluble proteins. Nearly one-third of the soluble proteins are predicted to be 
      recognized by this pathway, yet only a minor fraction of this proteome has been 
      identified as CMA substrates in cancer cells. Here, we undertook a quantitative 
      multiplex mass spectrometry approach to study the proteome of isolated lysosomes 
      in cancer cells during CMA-activated conditions. By integrating bioinformatics 
      analyses, we identified and categorized proteins of multiple cellular pathways 
      that were specifically targeted by CMA. Beyond verifying metabolic pathways, we 
      show that multiple components involved in select biological processes, including 
      cellular translation, was specifically targeted for degradation by CMA. In 
      particular, several proteins of the translation initiation complex were 
      identified as bona fide CMA substrates in multiple cancer cell lines of distinct 
      origin and we show that CMA suppresses cellular translation. We further show that 
      the identified CMA substrates display high expression in multiple primary cancers 
      compared to their normal counterparts. Combined, these findings uncover cellular 
      processes affected by CMA and reveal a new role for CMA in the control of 
      translation in cancer cells. Abbreviations: 6-AN: 6-aminonicotinamide; ACTB: 
      actin beta; AR7: atypical retinoid 7; CHX: cycloheximide; CMA: chaperone-mediated 
      autophagy; CQ: chloroquine; CTS: cathepsins; DDX3X: DEAD-box helicase 3 X-linked; 
      EEF2: eukaryotic translation elongation factor 2; EIF4A1: eukaryotic translation 
      initiation factor 4A1; EIF4H: eukaryotic translation initiation factor 4H; GEO: 
      Gene Expression Omnibus; GO: Gene Ontology; GSEA: gene set enrichment analysis; 
      HK2: hexokinase 2; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; 
      LAMP: lysosomal-associated membrane protein; LDHA: lactate dehydrogenase A; NES: 
      normalized enrichment score; NFKBIA: NFKB inhibitor alpha; PCA: principle 
      component analysis; PQ: paraquat; S.D.: standard deviation; SUnSET: surface 
      sensing of translation; TMT: tandem mass tags; TOMM40/TOM40: translocase of outer 
      mitochondrial membrane 40.
FAU - Hao, Yuqing
AU  - Hao Y
AUID- ORCID: 0000-0002-1910-0664
AD  - a Department of Physiology and Pharmacology, Biomedicum, Karolinska Institutet , 
      Stockholm , Sweden.
FAU - Kacal, Merve
AU  - Kacal M
AD  - a Department of Physiology and Pharmacology, Biomedicum, Karolinska Institutet , 
      Stockholm , Sweden.
FAU - Ouchida, Amanda Tomie
AU  - Ouchida AT
AD  - a Department of Physiology and Pharmacology, Biomedicum, Karolinska Institutet , 
      Stockholm , Sweden.
FAU - Zhang, Boxi
AU  - Zhang B
AD  - a Department of Physiology and Pharmacology, Biomedicum, Karolinska Institutet , 
      Stockholm , Sweden.
FAU - Norberg, Erik
AU  - Norberg E
AD  - a Department of Physiology and Pharmacology, Biomedicum, Karolinska Institutet , 
      Stockholm , Sweden.
FAU - Vakifahmetoglu-Norberg, Helin
AU  - Vakifahmetoglu-Norberg H
AD  - a Department of Physiology and Pharmacology, Biomedicum, Karolinska Institutet , 
      Stockholm , Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190320
PL  - United States
TA  - Autophagy
JT  - Autophagy
JID - 101265188
RN  - 0 (EIF4H protein, human)
RN  - 0 (Eukaryotic Initiation Factor-4F)
RN  - 0 (Eukaryotic Initiation Factors)
RN  - 0 (HSC70 Heat-Shock Proteins)
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
RN  - 0 (Proteome)
RN  - EC 3.6.1.- (DDX3X protein, human)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
SB  - IM
MH  - Cell Line, Tumor
MH  - Chaperone-Mediated Autophagy/drug effects/*genetics
MH  - DEAD-box RNA Helicases/genetics/metabolism
MH  - Eukaryotic Initiation Factor-4F/genetics/metabolism
MH  - Eukaryotic Initiation Factors/genetics/metabolism
MH  - Gene Ontology
MH  - HSC70 Heat-Shock Proteins/metabolism
MH  - Humans
MH  - Lysosomal-Associated Membrane Protein 2/metabolism
MH  - Lysosomes/enzymology/genetics/*metabolism
MH  - Neoplasms/genetics/*metabolism
MH  - Protein Biosynthesis/drug effects/*genetics
MH  - Proteolysis
MH  - Proteome/genetics/*metabolism
PMC - PMC6693453
OTO - NOTNLM
OT  - Autophagy
OT  - degradome
OT  - lysosome
OT  - proteome
OT  - translation
EDAT- 2019/03/02 06:00
MHDA- 2020/07/07 06:00
PMCR- 2019/03/20
CRDT- 2019/03/02 06:00
PHST- 2019/03/02 06:00 [pubmed]
PHST- 2020/07/07 06:00 [medline]
PHST- 2019/03/02 06:00 [entrez]
PHST- 2019/03/20 00:00 [pmc-release]
AID - 1586255 [pii]
AID - 10.1080/15548627.2019.1586255 [doi]
PST - ppublish
SO  - Autophagy. 2019 Sep;15(9):1558-1571. doi: 10.1080/15548627.2019.1586255. Epub 
      2019 Mar 20.