KEY RESOURCES TABLE
| REAGENT or RESOURCE | SOURCE | IDENTIFIER |
|---|---|---|
| Antibodies | ||
| Rabbit monoclonal anti-p21 | Cell Signaling Technologies | Cat# 2947, RRID:AB_823586 |
| Rabbit monoclonal anti-p16 | Cell Signaling Technologies | Cat# 80772, RRID:AB_2799960 |
| Rabbit polyclonal CyclinB1 | Cell Signaling Technologies | Cat# 4138, RRID:AB_2072132 |
| Rabbit monoclonal anti-CyclinD1 | Cell Signaling Technologies | Cat# 2978, RRID:AB_2259616 |
| Mouse monoclonal anti-CyclinE1 | Cell Signaling Technologies | Cat# 4129, RRID:AB_2071200 |
| Rabbit polyclonal anti-Cleaved Caspase 3 | Cell Signaling Technologies | Cat# 9661, RRID:AB_2341188 |
| Rabbit monoclonal anti-phospho-mTOR | Cell Signaling Technologies | Cat# 5536, RRID:AB_10691552 |
| Rabbit monoclonal anti-mTOR | Cell Signaling Technologies | Cat# 2983, RRID:AB_2105622 |
| Rabbit polyclonal anti-phospho-S6K | Cell Signaling Technologies | Cat# 9205, RRID:AB_330944 |
| Rabbit polyclonal anti-S6K | Cell Signaling Technologies | Cat# 9202, RRID:AB_331676 |
| Rabbit polyclonal anti-phospho-S6 | Cell Signaling Technologies | Cat# 2211, RRID:AB_331679 |
| Rabbit monoclonal anti-S6 | Cell Signaling Technologies | Cat# 2217, RRID:AB_331355 |
| Rabbit polyclonal anti-phospho-eIF2a | Cell Signaling Technologies | Cat# 9721, RRID:AB_330951 |
| Rabbit monoclonal anti-eIF2a | Cell Signaling Technologies | Cat# 5324, RRID:AB_10692650 |
| Rabbit monoclonal anti-Sestrin2 | Cell Signaling Technologies | Cat# 8487, RRID:AB_11178663 |
| Rabbit polyclonal anti-AMPKa | Cell Signaling Technologies | Cat# 2532, RRID:AB_330331 |
| Rabbit monoclonal anti-phospho-AMPK | Cell Signaling Technologies | Cat# 2535, RRID:AB_331250 |
| Rabbit polyclonal anti-p62 | Cell Signaling Technologies | Cat# 5114, RRID:AB_10624872 |
| Rabbit polyclonal anti-LC3B | Cell Signaling Technologies | Cat# 2775, RRID:AB_915950 |
| Rabbit monoclonal anti-GAPDH | Cell Signaling Technologies | Cat# 2118, RRID:AB_561053 |
| Goat anti-rabbit IgG HRP-linked | Cell Signaling Technologies | Cat# 7074, RRID:AB_2099233 |
| Horse anti-mouse IgG HRP-linked | Cell Signaling Technologies | Cat# 7076, RRID:AB_330924 |
| Mouse monoclonal anti-ASS1 | Abcam | Cat# ab124465, RRID:AB_10975633 |
| Rabbit monoclonal anti-OTC | Abcam | Cat# ab203859, RRID:AB_2876368 |
| Rabbit monoclonal anti-CPS1 | Abcam | Cat# ab129076, RRID:AB_11156290 |
| Rabbit monoclonal anti-GCN2 | Abcam | Cat# ab134053, RRID:AB_2890925 |
| Rabbit monoclonal anti-phospho-GCN2 | Abcam | Cat# ab75836, RRID:AB_1310260 |
| Rabbit monoclonal anti-p21 | Abcam | Cat# ab188224, RRID:AB_2734729 |
| Mouse monoclonal anti-ASL | Invitrogen | Cat# MABE343, RRID:AB_2566826 |
| Mouse monoclonal anti-p27 | SantaCruz Biotechnology | Cat# sc-1641, RRID:AB_628074 |
| Rabbit polyclonal anti-CREB-2/ATF4 | SantaCruz Biotechnology | Cat# sc-22800, RRID:AB_2058742 |
| Rabbit polyclonal anti-ASS1 | SantaCruz Biotechnology | Cat# sc-99178, RRID:AB_2060474 |
| Rabbit polyclonal anti-SLC7A1/CAT1 | Thermo Fisher Scientific | Cat# PA5-90039, RRID:AB_2805903 |
| Rat monoclonal anti-Ki67-FITC | Thermo Fisher Scientific | Cat# 11-5698-82, RRID:AB_11151330 |
| Mouse monoclonal anti-puromycin antibody | Millipore | Cat# MABE343, RRID:AB_2566826 |
| Rabbit monoclonal anti-Arg1 | Sigma-Aldrich | Cat# 380R-14, RRID:AB_2890926 |
| Goat biotinylated goat anti-Rabbit | Vector Laboratories | Cat# BA-1000, RRID:AB_2313606 |
| Bacterial and virus strains | ||
| Biological samples | ||
| HCC tumor and healthy liver samples | CHTN | N/A |
| Hepatocellular carcinoma tissue array | US Biomax | Cat# LV245 |
| Chemicals, peptides, and recombinant proteins | ||
| RPMI | GIBCO | Cat# 11-875-093 |
| Standard FBS | Gemini | Cat# 100-108 |
| Dialyzed FBS | Gemini | Cat# 900-108 |
| RPMI for SILAC | Thermo Fisher Scientific | Cat# 88365 |
| Propidium Iodide | Thermo Fisher Scientific | Cat# P3566 |
| ProLong Diamond Antifade Mountant with DAPI | Thermo Fisher Scientific | Cat# P36962 |
| Halt Protease and Phosphatase Inhibitor Cocktail | Thermo Fisher Scientific | Cat# 78445 |
| RNase A | Thermo Fisher Scientific | Cat# EN0531 |
| EcoLite (+)™ Liquid Scintillation Cocktail | Thermo Fisher Scientific | Cat# SKU 0188247501 |
| FuGENE 6 Transfection Reagent | Promega | Cat# E2691 |
| Control diet | Teklad Envigo | Cat# TD.01084 |
| Arg free diet | Teklad Envigo | Cat# TD.09152 |
| GCN2iB | MedChem Express | Cat# HY-112654 |
| ABT-263 | AdooQ BioScience | Cat# A10022 |
| Arginine Monohydrochloride L-[2,3,4-3H] | Perkin Elmer | Cat# NET1123250UC |
| Nuclear Fast Red | Sigma-Aldrich | Cat# N3020 |
| N-Ethylmaleimide | Sigma-Aldrich | Cat# E3876 |
| Arginine | Sigma-Aldrich | Cat# A8094 |
| Serine | Sigma-Aldrich | Cat# S4500 |
| EmbryoMax® Nucleosides (100X) | Fisher Scientific | Cat# ES-008-D |
| L-Aspartic acid | Sigma-Aldrich | Cat# A7219 |
| Deoxynucleotide Set | Sigma-Aldrich | Cat# DNTP100-1KT |
| ATP | Sigma-Aldrich | Cat# A1852 |
| Critical commercial assays | ||
| FITC Annexin V Apoptosis Detection Kit | BD Biosciences | Cat# 556547 |
| RNeasy Mini Kit | Qiagen | Cat# 74104 |
| High-Capacity cDNA Reverse Transcription Kit | Applied Biosystems | Cat# 4368814 |
| TaqMan Fast Advanced Master Mix | Applied Biosystems | Cat# 4444965 |
| Click-iT™ Plus EdU Alexa Fluor™ 488 Flow Cytometry Assay Kit | Thermo Fisher Scientific | Cat# C10633 |
| BCA protein assay kit | Thermo Fisher Scientific | Cat# 23225 |
| Autophagy detection kit | Abcam | Cat# ab139494 |
| Vectastain Elite ABC kit | Vector Laboratories | Cat# PK6100 |
| DAB peroxidase substrate kit | Vector Laboratories | Cat# SK4100 |
| ATP Determination Kit | Thermo Fisher Scientific | Cat# A22066 |
| ADP/ATP ration determination kit | Sigma-Aldrich | Cat# MAK135 |
| Arginine determination kit | Biovision | Cat# K384-100 |
| Ammonia determination kit | Biovision | Cat# K370-100 |
| XF Cell Mito Stress Test Kit | Agilent Technologies | Cat# 103015-100 |
| Deposited data | ||
| Experimental models: cell lines | ||
| Human: 293T | ATCC | Cat# CRL-3216, RRID:CVCL_0063 |
| Human: SNU-182 | ATCC | Cat# CRL-2235, RRID:CVCL_0090 |
| Human: SNU-398 | ATCC | Cat# 00398, RRID:CVCL_0077 |
| Human: SNU-423 | ATCC | Cat# CRL-2238, RRID:CVCL_0366 |
| Human: SNU-449 | ATCC | Cat# 00449, RRID:CVCL_0454 |
| Human: SNU-475 | ATCC | Cat# CRL-2236, RRID:CVCL_0497 |
| Human: Huh7 | ATCC | Cat# CCLV-1079, RRID:CVCL_0336 |
| Human: Hep3B | ATCC | Cat# HB-8064, RRID:CVCL_0326 |
| Human: HepG2 | ATCC | Cat# HB-8065, RRID:CVCL_0027 |
| Human: PC-3 | ATCC | Cat# CRL-1435 |
| Human: MDA-MB-231 | ATCC | Cat# CRM-HTB-26 |
| Human: SK-LMS-1 | ATCC | Cat# HTB-88 |
| Human: Primary hepatocytes | Sekisui XenoTech | Cat# H1500 |
| Mouse: Hep55.1c | Cell Line Service | Cat# 400201 |
| Mouse: HepaMP-4 | Generated in-house | N/A |
| Mouse: HepaMP-9-1 | Generated in-house | N/A |
| Experimental models: organisms/strains | ||
| Balb/c CAnN.Cg-Foxn1nu/Crl mice | Charles River | Cat# Strain-194 |
| C57BL/6J mice | JAX | Cat# 000664 |
| Oligonucleotides | ||
| Sybr Green Primers for qRT-PCR, see Table S1 | This paper | N/A |
| TaqMan primerset: ASS1 | Life Technologies | Cat# Hs01597989_g1 |
| TaqMan primerset: ALS | Life Technologies | Cat# Hs00902699_m1 |
| TaqMan primerset: ARG1 | Life Technologies | Cat# Hs00968979_m1 |
| TaqMan primerset: OTC | Life Technologies | Cat# Hs00166892_m1 |
| TaqMan primerset: CPS1 | Life Technologies | Cat# Hs00157048_m1 |
| TaqMan primerset: CDKN1A/p21 | Life Technologies | Cat# Hs00355782_m1 |
| TaqMan primerset: CCNB1 | Life Technologies | Cat# Hs01030099_m1 |
| TaqMan primerset: CCND1 | Life Technologies | Cat# Hs00765553_m1 |
| TaqMan primerset: CCNE1 | Life Technologies | Cat# Hs01026536_m1 |
| TaqMan primerset: SESN2 | Life Technologies | Cat# Hs00230241_m1 |
| TaqMan primerset: CDKNA2/p16 | Life Technologies | Cat# Hs00923894_m1 |
| TaqMan primerset: CDKN1B/p27 | Life Technologies | Cat# Hs00153277_m1 |
| Recombinant DNA | ||
| CDKN1A/p21 shRNA #1 | DharmaconTM | Cat# TRCN0000040123 |
| CDKN1A/p21 shRNA #2 | DharmaconTM | Cat# TRCN0000040124 |
| SLC7A1 shRNA #4 | DharmaconTM | Cat# TRCN0000042965 |
| SLC7A1 shRNA #5 | DharmaconTM | Cat# TRCN0000042966 |
| hEAAT | Ochocki, et al. 2018 | N/A |
| MGC Fully Sequenced Human ASS1 cDNA | Open Biosystems | Cat# MHS1010-202694229 |
| Software and algorithms | ||
| GraphPad PRISM 9.0.0 | GraphPad | N/A |
| ImageJ 2.1.0/1.53c | Open source processing software | N/A |
| FlowJo 10.6.2 Software | FlowJo LLC | N/A |
| Other | ||
| Leica Microscope | Leica Biosystems | DM5000B |
| BD FACS Calibur | BD Biosciences | N/A |
| ViiA7 Real-Time PCR system | Applied Biosystems | N/A |
| Tissue Tearer | Biospec | Cat# 985370 |
| Countess Automated Cell Counter | Invitrogen | Cat# C10281 |