REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
4EBP1 mAb (Rabbit)	Cell Signaling Technology	Cat# 9644; RRID:AB_2097841
4EBP1 (T37/46P) mAb (Rabbit)	Cell Signaling Technology	Cat# 2855; RRID:AB_560835
AKT1 antibody (Rabbit)	Cell Signaling Technology	Cat# 9272; RRID:AB_329827
AKT1 (S473P) mAb (Mouse)	Cell Signaling Technology	Cat# 4051; RRID:AB_331158
AKT1 (T308P) antibody (Rabbit)	Cell Signaling Technology	Cat# 9275; RRID:AB_329828
AKT2 antibody (Rabbit)	Cell Signaling Technology	Cat# 2962; RRID:AB_329872
AKT3 antibody (Rabbit)	Cell Signaling Technology	Cat# 4059; RRID:AB_2225351
Anti-p21 Antibody (F-5) (Mouse)	Santa Cruz Biotechnology	Cat# sc-6246; RRID:AB_628073
Anti-puromycin antibody (Mouse)	Millipore	Cat# MABE343; RRID:AB_2566826
BAD mAb (Rabbit)	Cell Signaling Technology	Cat# 9239; RRID:AB_2062127
BAX mAb (Rabbit)	Cell Signaling Technology	Cat# 5023; RRID:AB_10557411
Bcl2 mAb (Rabbit)	Cell Signaling Technology	Cat# 4223; RRID:AB_1903909
β-Actin (13E5) mAb (Rabbit)	Cell Signaling Technology	Cat# 4970; RRID:AB_2223172
Bim mAb (Rabbit)	Cell Signaling Technology	Cat# 2933; RRID:AB_1030947
Caspase 3 (Rabbit)	Cell Signaling Technology	Cat# 9662; RRID:AB_331439
Caspase 8 mAb (Rabbit)	Cell Signaling Technology	Cat# 4790; RRID:AB_10545768
Cleaved caspase 3 (Rabbit)	Cell Signaling Technology	Cat# 9664; RRID:AB_2070042
Cleaved caspase 8 mAb (Rabbit)	Cell Signaling Technology	Cat# 8592; RRID:AB_10891784
Cleaved PARP1 mAb (Rabbit)	Cell Signaling Technology	Cat# 5625; RRID:AB_10699459
DR5 mAb (Rabbit)	Cell Signaling Technology	Cat# 8074; RRID:AB_10950817
GAPDH mAb (Rabbit)	Cell Signaling Technology	Cat# 8884; RRID:AB_11129865
IgG (Rabbit)	Sigma-Aldrich	Cat# GENA934, RRID:AB_2722659
IgG2a, kappa Isotype Control Antibody (Mouse)	Biolegend	Cat# 401502; RRID:AB_2800437
mTOR (Rabbit)	Cell Signaling Technology	Cat# 2983; RRID:AB_2105622
mTOR (S2448P) mAb (Rabbit)	Cell Signaling Technology	Cat# 5536; RRID:AB_10691552
p53 (Mouse)	Santa Cruz Biotechnology	Cat# sc-126; RRID:AB_628082
PARP1 mAb (Rabbit)	Cell Signaling Technology	Cat# 9532; RRID:AB_659884
PP2AC mAb (Rabbit)	Cell Signaling Technology	Cat# 2259; RRID:AB_561239
PUMA (Rabbit)	Cell Signaling Technology	Cat# 98672; RRID:N/A
Chemicals, peptides, and recombinant proteins
10x Tris/glycine buffer	Bio-Rad	Cat# 1610734
10x Tris/glycine/SDS buffer	Bio-Rad	Cat# 1610732
5-FU (99% HPLC purified)	Sigma-Aldrich	Cat# F6627
BCA protein assay kit	Thermo-Scientific	Cat# 23225
Bolt LDS sample buffer (4X)	Life Technologies	Cat# B0007
Cell Dissociation Buffer, enzyme-free	Thermo-Scientific	Cat#13151014
Cycloheximide	Sigma-Aldrich	Cat# 01810
Halt Protease and Phosphatase inhibitor cocktail	Thermo-Scientific	Cat# 78440
Immobilon-P (PVDF) membrane	Merck Millipore	Cat# IPVH00010
Mini-PROTEAN TGX precast gel 4–15%	Bio-Rad	Cat# 456–1085
Muse Caspase-3/7 kitEMD	Millipore	Cat# MCH100108
MTT (3-(4,5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide)	Fisher Scientific	Cat# M6494
Oxaliplatin	TOCRIS Biosciences	Cat# 2623
PBS with 0.5% Tween 20 pH 7.4	Sigma-Aldrich	Cat# P3563
Phosphate Buffer Saline	Sigma-Aldrich	Cat# P-5368
Pierce RIPA buffer	Thermo-Scientific	Cat# 89901
Protein A/G PLUS-Agarose	Santa Cruz Biotechnology	Cat# sc-2003
Puromycin dihydrochloride	Santa Cruz Biotechnology	Cat# sc-108071A
rPP2A-Cα (recombinant)	Cayman Chemical	Cat# 10011237
Threonine phosphopeptide (KRpTIRR)	MilliporeSigma	Cat# 12-219
TRAIL/Apo2l	PreproTech, Inc.	Cat# 310-04
TRIZOL reagent	Life Technologies	Cat# 15596
Trypsin/EDTA (0.05%)	Thermo-Scientific	Cat# 25300054
Deposited data
RNAseq data of FOLFOX-resistant HT29 cells	This paper: https://doi.org/10.5281/zenodo.6565046	Zenoda data: https://zenodo.org/record/6565046#.YobdkKjMJPY
TCGA data were for CRC cells	This paper: https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga/studied-cancers/colorectal	Cancer Genome Atlas: https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga/studied-cancers/colorectal
Gene expression data for FOLFOX-resistant and non-resistant patient	This paper: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72970	NCBI Gene expression Omnibus (GEO) under GSE72970 accession: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72970
Experimental models: Cell lines
FHC	ATCC	N/A
FOLFOX-resistant HCT116	Adhip P. Majumdar, John D. Dingell VA Medical Centre, Detroit, MI	N/A
FOLFOX-resistant HT29	Adhip P. Majumdar, John D. Dingell VA Medical Centre, Detroit, MI	N/A
HCT116	ATCC	N/A
HCT116-p21−/− cells	Bert Vogelstein, Johns Hopkins Medical School, Baltimore, MD	N/A
HCT116-p21−/−/H6p21 cells	Brian K. Law, University of Florida, Gainesville, FL	N/A
HT-29	ATCC	N/A
LoVo	ATCC	N/A
LS174T	ATCC	N/A
RKO	ATCC	N/A
SW480	ATCC	N/A
Oligonucleotides
actin B-F (GCTCCTCCTGAGCGCAAGTACTC	Sigma-Aldrich	N/A
actin B-R (GTGGACAGCGAGGCCAGGAT)	Sigma-Aldrich	N/A
p21-F- (CCGCGACTGTGATGCGCTAATG)	Sigma-Aldrich	N/A
p21-R (CTCGGTGACAAAGTCGAAGTTC)	Sigma-Aldrich	N/A
TP53-F (CACATGACGGAGGTTGTGAG)	Sigma-Aldrich	N/A
TP53-R (ACACGCAAATTTCCTTCCAC)	Sigma-Aldrich	N/A
Software and algorithms
CalcuSyn	Biosoft	http://www.biosoft.com/w/calcusyn.htm
GraphPad Prism v8.0	Dotmatics	N/A
ImageJ	NIH Image	N/A
Sigma-Plot 9	Systat Software, Inc.	N/A