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. 2020 Mar 13;10:322. doi: 10.3389/fonc.2020.00322

Table 2.

ATG mRNAs expression regulated by translation machinery.

Protein Studied Model Autophagy evaluation Autophagy flux assessment Additional observations References
4E-BP1 LHMB-AR
PrEC
sh4E-BP1
↑LC3-II, ↑acridine orange (37) #122
4E-BP1 HL60 or HeLa parthenolide
HEK293
Parthenolide +
sh4E-BP1
HeLa
Parthenolide + plasmid 4E-BP1
↑LC3-II, ↑GFP-LC3
↑LC3-II
↓LC3-II
↓ 4EB-P1
↓Ⓟ 4E-BP1
(38) #127
4EB-P1 HCT-1116
hypoxia
↑ translation 35 lysosomal mRNAs
↑ acridine orange
↑ LysoTracker+
↑ LC3-II
↓p62
↑Ⓟ eIF2α;
↓Ⓟ 4EB-P1
↑ translation EIF4EBP3 and EIF2AK3;
EIF4E, RPS6K subunits
(39) #40
4E-BP1
Akt
S6K1
HepG2.2.15
si4E-BP1
siAkt or Akt inhibitors
siS6K1
↑LC3-II
↓LC3-II ↓GFP-LC3 puncta ↑p62
↓LC3-II
CQ ↑ LC3-II
CQ ≠ LC3-II
(40) #161
eIF4E T-ALL Jurkat
selenite
selenite +sieIF4E
↑LC3-II ↑GFP-LC3 puncta
↑ATF4 on MAP1LC3B and CHOP promoters
↓GFP-LC3 puncta
↓ATF4 on MAP1LC3B and CHOP promoters
Baf A1
↑LC3-II ↑p62
↑CHOP, ↑Ⓟ eIF4E
↓ATF4
+ si_p38 or p38 inhibitors prevent selenite effects
(41) #124
eIF4E
eIF2α
NB-4
selenite
selenite+ sieIF2α
selenite+ plasmid eIF4E
↓LC3-II, ↑p62
↓GFP-LC3 puncta
↓ATF4 on MAP1LC3B promoter
↑LC3-II, ≠GFP-LC3
↑LC3-II ↑GFP-LC3 puncta
↑ATF4 on MAP1LC3B promoter
↑CHOP, ↑ATF4 ↑Ⓟ eIF2α, ↓Ⓟ eIF4E
↓CHOP
↑CHOP
(42) #43
eIF5A eIF4A3 MCF-7
sieIF5A
sieIF5A +Torin-1
↓GFP-LC3 puncta ↓autophagosome (TEM)
↓ATG3
↓GFP-LC3 puncta
Baf A1 ↑LC3-II (43)
iff-2
(eIF5A homlog)
C. elegans iff-2 RNAi ↓GFP::LGG-1 puncta (43)
eIF4G1 eIF4G2 MCF10A or HEK293T
sheIF4G1 or
sh eIF4G2
↑LC3-II ↑GFP-LC3 puncta ↑MDC+ Vesicles (44) #216
eIF4G1 MCF10A
sheIF4G1
γ irradiation
↑LC3-II ↑GFP-LC3 puncta (45) #2
RACK1 HT1080
siRACK1
HepG2, Hep3B, U2OS, HeLa, MCF-7 and MDAMB231
↑LC3-II
↑LAMP1 and LAMP2 ↑GFP-LC3 puncta and colocalization with LysoTracker
↑BCL-XL and BECN1 interaction
↓p62
↑polysomal fraction on MAP1LC3 and BCL-XL mRNA
Baf A1
↑LC3-II
↑p62
(46) #126
RPS27L MB231 or SK-BR3+ siRPS27L ↑LC3-II ↑EGFP-LC3 puncta
↓p62
+CQ or Baf A1: ↑LC3-II and ↑p62 ↑DEPTOR, ↓Ⓟ S6K1 and Ⓟ 4EBP1
↓Ⓟ S6K1 and Ⓟ 4EBP1
(47) #131
MEFs RSP27L−/− ↑LC3-II
↓p62
HuD βTC6 or U2OS
siHuD
plasmid HuD
≠ATG5 mRNA; ↓ATG5 ↓LC3-II ↓GFP-LC3 puncta
↓autophagosomes (TEM)
≠ATG5 mRNA ↑ATG5 ↑LC3-II ↑GFP-LC3 puncta
+miR-181 ↓EGFP-3'UTR Atg5 mRNA
↑EGFP-3'UTR Atg5 mRNA
(48) #125
HuR HSC-LX2 or HSC-T6
erastin+ siHuR
HSC-LX2 or HSC-T6
erastin+ plasmid HuR
↓LC3-II ↓BECN1 ↑p62
↑LC3-II ↑BECN1 ↑autophagosome (TEM), ↓p62
CQ: ↑LC3-II RIP: 3'UTR BECN1 mRNA enrichment (49)
HuR L-02 or Hep3B
siHuR
↓ATG5, ATG12 and ATG16
↓polysome association to ATG5, ATG12 and ATG16 mRNAs
↓LC3-II
↓Autophagosome and autolysosome (TEM)
↓GFP-LC3 puncta
colchicine modest ↑LC3-II RIP: 3'UTR ATG5, ATG12, ATG16 mRNAs enrichment (50) #36
HuR HK-2
hypoxia
HK-2
hypoxia+ shHuR
↑LC3-II, ATG7 and ATG16
↓LC3-II, ATG7 and ATG16
↑TUNEL+ cells
RIP: ATG7, ATG16 mRNAs enrichment
(51)
HuR MCF-7
starvation
MCF-7, MDA-MB 231, PC3, HaCat
siHur
↑LC3-II, ↑BECN1, ↑polysomes association of BECN1 mRNA & HuR,
↓LC3-II
↓BECN1
BECN1 mRNA
RIP: 3'UTR BEC1 mRNA enrichment (52)
HuR Intestinal epithelium IE_HuR−/− mice ↓LC3-II ↓BECN1, ↓ATG16L1 ↓ATG7 RIP: ATG16 mRNA
enrichment
(53)
IECs
siHuR
↓LC3-II ↓ATG16L1
↓ newly synthesized ATG16L1
ZFP36 HSC-LX2 or HSC-T6 erastin
+ plasmid ZFP36
↓ LC3-II ↓GFP-LC3 puncta
↓ ATG16L1
↓ ATG5-ATG12
↓ Autophagosome (TEM)
ATG16 mRNA, ↑SQSTM11 mRNA
RIP: ATG16 mRNA enrichment
Luc-3'ÚTR Atg16 mRNA:
↓Luc activity
(54)
HSC-LX2 or HSC-T6 erastin
+ plasmid FXBW7
↑ LC3-II, ↑ ATG16L1, ↑ ATG5-ATG12
↑ Autophagosome (TEM)
hnRNPA1 HCT-116
sihnRNPA1
plasmid hnRNPA1
↓BECN1, ≠ Becn1 mRNA
↑BECN1, ≠ Becn1 mRNA
Luc-3′ÚTR Becn1 mRNA: ↓Luc activity
Luc-3′ÚTR Becn1 mRNA: ↑ Luc activity
Biotin-3′UTR Benc1 mRNA
RIP: Becn1 mRNA enrichment
(55)
Orb Drosophila germarium Orb mutant Atg12 (mRNA); ↑Atg12 and Atg8 (protein);
↑LysoTracker+ structures
RIP: Atg12 mRNA enrichment (56) #8
Dhh1 (DDX6) Yeast Δdhh1
nutrient replete
↑ Atg3, Atg7, Atg8, Atg19, Atg20, Atg22 and Atg24 mRNA GFP- ATG8 processing assay Δdhh1+ starvation: ↑ GFP free (57) #123
Mouse ESC
DDX6 +/−
↑Map1lc3 mRNA
↑LC3-II ↓LC3 puncta
↓p62
HeLa+ siDDX6 ↑ MAP1LC3 mRNA
↑ LC3 puncta
HeLa+ plasmid DDX6 MAP1LC3 mRNA
↓ LC3-II ↓LC3 puncta ↑p62
Dhh1 (DDX6) Eap1 Yeast Δdhh1
Nitrogen starvation
HEK293A DDX6 −/−
Amino acid starvation
↓Atg1, Atg13 (protein)
ATG1 and ATG13 mRNAs
↓ATG16L1
ATG16L1 mRNA
Pgi-GFP processing assay:
↓ free GFP
(58) #24 ó 1
Psp2 Yeast Δpsp2+ Nitrogen starvation ↓Atg1 ≠ ATG1 mRNA ↓polysomes association of ATG1 mRNA, ↓Atg13 Pgi-GFP processing assay:
↓ free GFP
Pho8Δ60 assay: ↓ vacuolar Pho8Δ60
RIP: ATG1 & ATG13 mRNA enrichment (59) #274
ATF4
CHOP
MEFs ATF4 /− leucine starvation Atg16l1, Map1lc3b, Atg12, Atg3, Becn1, Gabarapl2, p62, Nbr1, Atg7 mRNAs ↑Ⓟ eIF2α (60) #3
MEFs CHOP /− leucine starvation Atg10, Gabarap, Atg5, p62, Nbr1, Atg7 mRNAs ↑Ⓟ eIF2α
PERK
ATF4
LNCaP
Tunicamycin
↑ LC3-II
mTagRFP-mWasabi-LC3: ↑ red punctate
MAP1LC3B, GABARAPL1, WIPI1, MAPLC3B2, MAPLC3A, ATG13, ATG16L1, GAGARAP, ATG12, ATG5, ATG3, BECN1 mRNA
BafA1:
↑ LC3-II
mTagRFP-mWasabi-LC3: ↑ yellow puncta
LDH sequestration assay: ↑ sequestration rate
LLPD assay: ↑ Valine release
(61) #128
LNCaP
Tunicamycin
siATF4
MAP1LC3B, GABARAPL1, WIPI1, MAPLC3B2, MAPLC3A, ATG13 mRNA ↓↓ Valine release
eIF2α
ATF4
MEFs
eIF2Aα non-phosphorylable mutant
or ATF4/ Rapamycin
Map1lc3 and Atg5 mRNA
↓LC3-II and LC3 puncta
GFP-LC3 processing assay:
↓ free GFP
(62) #130