PMID- 23584676
OWN - NLM
STAT- MEDLINE
DCOM- 20130715
LR  - 20230815
IS  - 1552-4469 (Electronic)
IS  - 1552-4450 (Print)
IS  - 1552-4450 (Linking)
VI  - 9
IP  - 6
DP  - 2013 Jun
TI  - Chemical modulation of chaperone-mediated autophagy by retinoic acid derivatives.
PG  - 374-82
LID - 10.1038/nchembio.1230 [doi]
AB  - Chaperone-mediated autophagy (CMA) contributes to cellular quality control and 
      the cellular response to stress through the selective degradation of cytosolic 
      proteins in lysosomes. A decrease in CMA activity occurs in aging and in 
      age-related disorders (for example, neurodegenerative diseases and diabetes). 
      Although prevention of this age-dependent decline through genetic manipulation in 
      mice has proven beneficial, chemical modulation of CMA is not currently possible, 
      owing in part to the lack of information on the signaling mechanisms that 
      modulate this pathway. In this work, we report that signaling through retinoic 
      acid receptor alpha (RARalpha) inhibits CMA and apply structure-based chemical design to 
      develop synthetic derivatives of all-trans-retinoic acid to specifically 
      neutralize this inhibitory effect. We demonstrate that chemical enhancement of 
      CMA protects cells from oxidative stress and from proteotoxicity, supporting a 
      potential therapeutic opportunity when reduced CMA contributes to cellular 
      dysfunction and disease.
FAU - Anguiano, Jaime
AU  - Anguiano J
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, New York, USA.
FAU - Garner, Thomas P
AU  - Garner TP
FAU - Mahalingam, Murugesan
AU  - Mahalingam M
FAU - Das, Bhaskar C
AU  - Das BC
FAU - Gavathiotis, Evripidis
AU  - Gavathiotis E
FAU - Cuervo, Ana Maria
AU  - Cuervo AM
LA  - eng
SI  - PubChem-Substance/162010013
SI  - PubChem-Substance/162010014
SI  - PubChem-Substance/162010015
SI  - PubChem-Substance/162010016
SI  - PubChem-Substance/162010017
SI  - PubChem-Substance/162010018
SI  - PubChem-Substance/162010019
SI  - PubChem-Substance/162010020
SI  - PubChem-Substance/162010021
GR  - R00 HL095929/HL/NHLBI NIH HHS/United States
GR  - R01 AG021904/AG/NIA NIH HHS/United States
GR  - AG031782/AG/NIA NIH HHS/United States
GR  - R37 AG021904/AG/NIA NIH HHS/United States
GR  - AA020630/AA/NIAAA NIH HHS/United States
GR  - HL095929/HL/NHLBI NIH HHS/United States
GR  - R21 AA020630/AA/NIAAA NIH HHS/United States
GR  - K99 HL095929/HL/NHLBI NIH HHS/United States
GR  - P01 AG031782/AG/NIA NIH HHS/United States
GR  - AG021904/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130414
PL  - United States
TA  - Nat Chem Biol
JT  - Nature chemical biology
JID - 101231976
RN  - 0 (Molecular Chaperones)
RN  - 0 (Rara protein, mouse)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 5688UTC01R (Tretinoin)
RN  - 9007-49-2 (DNA)
RN  - S88TT14065 (Oxygen)
SB  - IM
EIN - Nat Chem Biol. 2013 Nov;9(11):746
MH  - Animals
MH  - *Autophagy
MH  - Binding Sites
MH  - Cytosol/metabolism
MH  - DNA/chemistry
MH  - Lysosomes/metabolism
MH  - Mice
MH  - Molecular Chaperones/*chemistry
MH  - Molecular Conformation
MH  - Molecular Dynamics Simulation
MH  - NIH 3T3 Cells
MH  - Oxygen/metabolism
MH  - Receptors, Retinoic Acid/metabolism
MH  - Retinoic Acid Receptor alpha
MH  - Tretinoin/*chemistry
PMC - PMC3661710
MID - NIHMS454928
COIS- Competing financial interests The authors declare that they have no competing 
      interests.
EDAT- 2013/04/16 06:00
MHDA- 2013/07/17 06:00
PMCR- 2013/12/01
CRDT- 2013/04/16 06:00
PHST- 2013/01/12 00:00 [received]
PHST- 2013/03/11 00:00 [accepted]
PHST- 2013/04/16 06:00 [entrez]
PHST- 2013/04/16 06:00 [pubmed]
PHST- 2013/07/17 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - nchembio.1230 [pii]
AID - 10.1038/nchembio.1230 [doi]
PST - ppublish
SO  - Nat Chem Biol. 2013 Jun;9(6):374-82. doi: 10.1038/nchembio.1230. Epub 2013 Apr 
      14.