REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rabbit monoclonal anti-4EBP1	Cell Signaling Technology	Cat# 9644; RRID:AB_2097841
Mouse monoclonal anti-alpha-tubulin	Millipore Sigma	Cat# T-5168; RRID:AB_477579
Mouse monoclonal anti-beta-Actin	Millipore Sigma	Cat# A5316; RRID:AB_476743
Rabbit monoclonal anti-AKT	Cell Signaling Technology	Cat# 4691; RRID:AB_915783
Rabbit monoclonal anti-phospho-AKT (Thr308)	Cell Signaling Technology	Cat# 2965; RRID:AB_2255933
Rabbit monoclonal anti-BAK	Cell Signaling Technology	Cat# 12105; RRID: AB_2716685
Rabbit polyclonal anti-BAX	Cell Signaling Technology	Cat# 12105; RRID: AB_10695870
Rabbit monoclonal anti-BCL-2	Abcam	Cat# ab182858; RRID:AB_2715467
Rabbit monoclonal anti-BCL-XL	Cell Signaling Technology	Cat# 2764; RRID: AB_2228008
Rabbit polyclonal anti-BID	Bethyl	Cat# A300-084A; RRID: AB_242505
Rabbit monoclonal anti-BIM	Cell Signaling Technology	Cat# 2933; RRID: AB_1030947
Mouse monoclonal anti-BIM	Santa Cruz	Cat# sc-374358; RRID: AB_10987853
Rabbit monoclonal anti-Cleaved Caspase-3	Cell Signaling Technology	Cat# 9664; RRID: AB_2070042
Rabbit monoclonal anti-Ki67	Abcam	Cat# ab16667; RRID: AB_302459
Rabbit monoclonal anti-MCL-1	Cell Signaling Technology	Cat# 5453; RRID: AB_10694494
Rabbit monoclonal anti-MCL-1	Abcam	Cat# ab32087; RRID: AB_776245
Rabbit polyclonal anti-PARP	Cell Signaling Technology	Cat# 9542; RRID: AB_2160739
Rabbit monoclonal anti-RICTOR	Cell Signaling Technology	Cat# 9476; RRID: AB_10612959
Rabbit monoclonal anti-p70 S6 Kinase	Cell Signaling Technology	Cat# 2708; RRID:AB_390722
Rabbit monoclonal anti-phospho-p70 S6 Kinase (Thr389)	Cell Signaling Technology	Cat# 9234; RRID:AB_2269803
Rabbit polyclonal anti-phospho-S6 (Ser235/236)	Cell Signaling Technology	Cat# 2211; RRID: AB_331679
Rabbit monoclonal anti-phospho-S6 (Ser235/236)	Cell Signaling Technology	Cat# 4858; RRID: AB_916156
Rabbit polyclonal anti-Vinculin	Cell Signaling Technology	Cat# 4650; RRID:AB_10559207
Anti-mouse IgG, HRP-linked Antibody	Cell Signaling Technology	Cat# 7076; RRID:AB_330924
Anti-rabbit IgG, HRP-linked Antibody	Cell Signaling Technology	Cat# 7074; RRID:AB_2099233
Anti-rabbit IgG HRP TrueBlot	Rockland	Cat# 18-8816-31; RRID: AB_2610847
Anti-normal Rabbit IgG	Cell Signaling Technology	Cat# 2729; RRID: AB_1031062
Chemicals, peptides, and recombinant proteins
Rapamycin, mTORC1 inhibitor (used for in vitro studies)	Millipore Sigma	Cat# 553210; CAS: 53123-88-9
Rapamycin, mTORC1 inhibitor (used for in vivo studies)	LC Laboratories	Cat# R-5000; CAS: 53123-88-9
Torin1, mTOR inhibitor	Tocris	Cat# 4247; CAS: 1222998-36-8
AZD2014, mTOR inhibitor	SelleckChem	Cat# S2783; CAS: 1009298-59-2
RapaLink-1, mTOR inhibitor	MedChem Express	Cat# HY-111373; CAS: 1887095-82-0
ABT-263	SelleckChem	Cat# S1001; CAS: 923564-51-6
ABT-199	SelleckChem	Cat# S8048; CAS: 1257044-40-8
WEHI-539	Cayman Chemical	Cat# 21478; CAS: 1431866-33-9
Q-VD-OPh	Cayman Chemical	Cat# 15260; CAS: 1135695-98-5
Cycloheximide	Millipore Sigma	Cat# 01810; CAS: 66-81-9
Actinomycin D	Millipore Sigma	Cat# A9415; CAS: 50-76-0
Puromycin	Millipore Sigma	Cat# P8833; CAS: 58-58-2
Doxycycline Hydrochloride	Millipore Sigma	Cat# D3447; CAS: 10592-13-9
Crystal violet	Millipore Sigma	Cat# C6158; CAS: 548-62-9
Trypan blue	Millipore Sigma	Cat #T8154; CAS:72-57-1
Critical commercial assays
CellTiter-Glo Luminescent Cell Viability Assay	Promega	Cat# G7573
FITC Annexin V Apoptosis Detection Kit I	BD Biosciences	Cat# 556547
SuperScript III First-Strand Synthesis System	ThermoFisher Scientific/Invitrogen	Cat# 18080051
Experimental models: Cell lines
Mouse: Tsc2+/+&Tsc2−/−p53−/− MEFs	Laboratory of David Kwiatkowski; Zhang et al. 2003	N/A
Mouse: Tsc2−/−p53+/+ 3T3 MEFs + TSC2	Laboratory of Brendan Manning; Huang et al. 2008	N/A
Mouse: Tsc2−/−p53+/+ 3T3 MEFs + Vector	Laboratory of Brendan Manning; Huang et al. 2008	N/A
Mouse: 105K	Laboratory of Lisa Henske; Filippakis et al. 2017	N/A
Mouse: 105K + TSC2	This study; Filippakis et al. 2017	N/A
Mouse: 105K + Vector	This study; Filippakis et al. 2017	N/A
Mouse: Rictor+/+&Rictor−/− MEFs	Laboratory of David Sabatini; Guertin et al. 2006	N/A
Mouse: Eif4ebp1/2+/+&Eif4ebp1/2−/− MEFs	Laboratory of David Sabatini	N/A
Mouse: Eif4ebp1/2+/+ MEFs + VECTOR	This study	N/A
Mouse: Eif4ebp1/2−/− MEFs + VECTOR	This study	N/A
Mouse: Eif4ebp1/2−/− MEFs + 4E-BP1	This study	N/A
Human: HEK-293T	ATCC	CRL-3216 RRID:CVCL_0063
Human: 97-1 + Vector	Laboratory of David Kwiatkowski; Guo et al. 2013	N/A
Human: SNU-886	Novartis Institutes for BioMedical Research	N/A
Human: PC3	ATCC	CRL-1435 RRID:CVCL_0035
Human: LNCaP	ATCC	CRL-1740 RRID:CVCL_1379
Experimental models: Organisms/strains
Mouse: C57BL/6J wild-type	The Jackson Laboratory	JAX 000664 RRID:IMSR_JAX:000664
Oligonucleotides
Primers for qPCR, see method details section.	IDT	N/A
Non-targeting control siRNA	Dharmacon/Horizon Discovery	Cat# D-001810-10-50
Mcl1 siRNA	Dharmacon/Horizon Discovery	Cat# L-062229-00-0005
Bcl2 siRNA	Dharmacon/Horizon Discovery	Cat# L-063933-00-0005
BCL-XL (Bcl2l1) siRNA	Dharmacon/Horizon Discovery	Cat# L-065142-00-0005
Recombinant DNA
psPAX2	Addgene	12260, RRID: Addgene_12260
pMD2.G	Addgene	12259, RRID: Addgene_12259
Mouse MCL-1 (cDNA amplified from plasmid)	Addgene	32980, RRID: Addgene_32980
Mouse 4E-BP1 cDNA	This study	N/A
Plasmid: PLJM1-EGFP	Addgene	19319, RRID: Addgene_19319
Plasmid: PLJM1-MCL1	This study	N/A
Plasmid: pTRIPZ-EGFP	Laboratory of Brendan Manning; Torrence et al. 2021	N/A
Plasmid: pTRIPZ-4EBP1	This study	N/A
Software and algorithms
Prism 9	GraphPad	RRID: SCR_002798
FlowJo	FlowJo	RRID: SCR_008520; https://www.flowjo.com/solutions/flowjo
ImageJ	Schneider et al. 2012	RRID: SCR_003070; https://imagej.nih.gov/ij/
Morpheus	Morpheus by Broad Institute	RRID: SCR_017386; https://software.broadinstitute.org/morpheus/
SynergyFinder	Ianevski et al. 2020	RRID: SCR_019318; https://synergyfinder.fimm.fi
QuPath	Bankhead et al. 2017	RRID: SCR_018257; https://qupath.github.io/
Other
Protein-A/G Beads Agarose Beads	ThermoFisher Scientific	Cat# 20421
Matrigel Basement Membrane Matrix	BD Biosciences	Cat# 356237