Ser351

Site Information
SsKEVDPsTGELQsL SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 14580829

In vivo Characterization
Methods used to characterize site in vivo:	immunoassay ( 5 , 23 ) , immunoprecipitation ( 17 , 18 , 23 ) , mutation of modification site ( 1 , 7 , 14 , 19 , 22 , 23 ) , phospho-antibody ( 1 , 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 20 , 21 , 23 ) , western blotting ( 1 , 2 , 4 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 )
Disease tissue studied:	liver cancer ( 14 , 18 , 23 ) , hepatocellular carcinoma ( 14 , 23 )
Relevant cell line - cell type - tissue:	'muscle, skeletal' ( 13 ) , 'neuron, cortical' ( 7 ) , 'neuron, cortical'-brain ( 15 ) , 293 (epithelial) ( 7 , 17 , 23 ) , 3T3 (fibroblast) ( 16 ) , brain ( 11 ) , C2C12 (myoblast) ( 13 ) , CD8+ (T lymphocyte) ( 5 ) , fibroblast ( 9 ) , heart ( 4 , 8 ) , HEK293T (epithelial) ( 1 , 18 ) , Hepa-1 (hepatic) ( 18 ) , Hepa-1c1c7 (hepatic) ( 12 ) , hepatocyte ( 23 ) , hepatocyte-liver ( 19 ) , HepG2 (hepatic) ( 18 ) , HLE (hepatic) ( 23 ) , HLF (hepatic) ( 23 ) , Huh1 (hepatic) ( 23 ) , Huh7 (hepatic) ( 14 , 23 ) , JHH-1 (hepatic) ( 23 ) , JHH-2 (hepatic) ( 23 ) , JHH-4 (hepatic) ( 23 ) , JHH-5 (hepatic) ( 23 ) , JHH-7 (hepatic) ( 23 ) , lens ( 10 ) , liver ( 21 ) , MEF (fibroblast) ( 1 , 11 , 12 , 17 , 18 , 22 , 23 ) , muscle ( 2 ) , myocyte-heart ( 6 ) , OUMS-29 (hepatocyte) ( 20 ) , synovium ( 9 )

Upstream Regulation
Regulatory protein:	AMPKA1 (mouse) ( 18 ) , C1QBP (human) ( 8 ) , GJA8 (mouse) ( 10 ) , NRF2 (human) ( 2 ) , NRF2 (mouse) ( 9 ) , PIK3C3 (human) ( 7 ) , PKAR1A (human) ( 6 ) , RPT2 (mouse) ( 21 ) , SQSTM1 (mouse) ( 11 )
Putative in vivo kinases:	AMPKA1 (human) ( 12 , 18 ) , CK1A (human) ( 1 ) , mTOR (human) ( 4 ) , PKCZ (mouse) ( 7 ) , TAK1 (mouse) ( 17 ) , ULK1 (human) ( 3 )
Kinases, in vitro:	mTOR (human) ( 23 ) , ULK1 (human) ( 3 )
Treatments:	(5Z)-7-oxozeaenol ( 7 ) , antibody ( 5 ) , arsenite ( 23 ) , bacterial infection ( 22 , 23 ) , bafilomycin_A ( 20 ) , chloroquine ( 1 ) , CK1-7 ( 7 ) , curcumin ( 7 ) , deferoxamine ( 16 ) , exercise training ( 13 ) , ezetimibe ( 18 ) , glucose_oxidase ( 14 ) , H2O2 ( 6 ) , high-fat diet ( 20 ) , HT-DNA ( 1 ) , ischemia/reperfusion ( 6 ) , isoproterenol ( 6 ) , LPS ( 4 ) , mechanical stress ( 13 ) , metformin ( 5 ) , methionine- and choline-deficient diet ( 18 ) , NaAsO2 ( 11 ) , niclosamide ( 12 ) , NKH_477 ( 6 ) , oleic_acid ( 20 ) , palmitate ( 12 ) , palmitoleic_acid ( 20 ) , PP242 ( 7 ) , rapamycin ( 5 , 23 ) , resatorvid ( 4 ) , SAR405 ( 7 ) , SB203580 ( 7 ) , Sinomenine ( 9 ) , siRNA ( 1 , 7 ) , SP600125 ( 7 ) , SSTC3 ( 1 ) , Torin1 ( 7 , 23 ) , U0126 ( 7 ) , valinomycin ( 23 ) , wortmannin ( 7 )

Downstream Regulation
Effects of modification on SQSTM1:	activity, induced ( 12 , 23 ) , enzymatic activity, induced ( 23 ) , intracellular localization ( 15 ) , molecular association, regulation ( 1 , 11 , 17 , 23 ) , phosphorylation ( 9 ) , protein stabilization ( 7 , 9 )
Effects of modification on biological processes:	autophagy, induced ( 1 , 4 , 6 , 12 , 14 , 15 , 16 , 21 , 23 ) , carcinogenesis, altered ( 2 ) , carcinogenesis, induced ( 23 ) , carcinogenesis, inhibited ( 5 ) , cell growth, induced ( 5 , 23 ) , signaling pathway regulation ( 2 , 3 , 6 , 9 , 23 ) , transcription, altered ( 11 ) , transcription, induced ( 1 , 3 , 5 , 6 , 7 , 22 , 23 ) , transcription, inhibited ( 19 )
Induce interaction with:	KEAP1 (human) ( 17 , 23 ) , KEAP1 (mouse) ( 11 ) , STING (human) ( 1 )

Disease / Diagnostics Relevance
Relevant diseases:	hepatocellular carcinoma ( 23 )

References
1	Pan M, et al. (2023) CSNK1A1/CK1α suppresses autoimmunity by restraining the CGAS-STING1 signaling. Autophagy, 1-18 37723657 Curated Info
2	Yamada M, et al. (2023) Muscle p62 stimulates the expression of antioxidant proteins alleviating cancer cachexia. FASEB J 37, e23156 37624620 Curated Info
3	Ikeda R, et al. (2023) Phosphorylation of phase-separated p62 bodies by ULK1 activates a redox-independent stress response. EMBO J, e113349 37306101 Curated Info
4	Matsuo I, et al. (2022) Role of TLR4 signaling on Porphyromonas gingivalis LPS-induced cardiac dysfunction in mice. PLoS One 17, e0258823 35648750 Curated Info
5	Nishida M, et al. (2021) Mitochondrial reactive oxygen species trigger metformin-dependent antitumor immunity via activation of Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8T lymphocytes. J Immunother Cancer 9 34531248 Curated Info
6	Liu Y, et al. (2021) Loss of PKA regulatory subunit 1α aggravates cardiomyocyte necrosis and myocardial ischemia/reperfusion injury. J Biol Chem 297, 100850 34087234 Curated Info
7	Park JY, Sohn HY, Koh YH, Jo C (2021) Curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at Ser351. Sci Rep 11, 8430 33875681 Curated Info
8	Yagi M, et al. (2021) Mitochondrial translation deficiency impairs NAD -mediated lysosomal acidification. EMBO J, e105268 33528041 Curated Info
9	Liao K, et al. (2021) Sinomenine protects bone from destruction to ameliorate arthritis via activating p62-Keap1-Nrf2 feedback loop. Biomed Pharmacother 135, 111195 33395605 Curated Info
10	Jara O, et al. (2020) p62/Sequestosome 1 levels increase and phosphorylation is altered in Cx50D47A lenses, but deletion of p62/sequestosome 1 does not improve transparency. Mol Vis 26, 204-215 32214786 Curated Info
11	Deng Z, et al. (2019) ALS-FTLD-linked mutations of SQSTM1/p62 disrupt selective autophagy and NFE2L2/NRF2 anti-oxidative stress pathway. Autophagy, 1-15 31362587 Curated Info
12	Park JS, Lee YS, Lee DH, Bae SH (2019) Repositioning of niclosamide ethanolamine (NEN), an anthelmintic drug, for the treatment of lipotoxicity. Free Radic Biol Med 137, 143-157 31035006 Curated Info
13	Yamada M, et al. (2019) p62/SQSTM1 and Nrf2 are essential for exercise-mediated enhancement of antioxidant protein expression in oxidative muscle. FASEB J, fj201900133R 30913396 Curated Info
14	Medvedev R, et al. (2017) HCV-induced oxidative stress by inhibition of Nrf2 triggers autophagy and favors release of viral particles. Free Radic Biol Med 110, 300-315 28673615 Curated Info
15	Ugun-Klusek A, et al. (2017) Continued 26S proteasome dysfunction in mouse brain cortical neurons impairs autophagy and the Keap1-Nrf2 oxidative defence pathway. Cell Death Dis 8, e2531 28055010 Curated Info
16	Inoue H, et al. (2017) Iron deficiency induces autophagy and activates Nrf2 signal through modulating p62/SQSTM. Biomed Res 38, 343-350 29225212 Curated Info
17	Hashimoto K, et al. (2016) TAK1 Regulates the Nrf2 Antioxidant System Through Modulating p62/SQSTM1. Antioxid Redox Signal 25, 953-964 27245349 Curated Info
18	Lee DH, et al. (2016) Ezetimibe, an NPC1L1 inhibitor, is a potent Nrf2 activator that protects mice from diet-induced nonalcoholic steatohepatitis. Free Radic Biol Med 99, 520-532 27634173 Curated Info
19	Popineau L, et al. (2016) Novel Grb14-Mediated Cross Talk between Insulin and p62/Nrf2 Pathways Regulates Liver Lipogenesis and Selective Insulin Resistance. Mol Cell Biol 36, 2168-81 27215388 Curated Info
20	Miyagawa K, et al. (2016) Lipid-Induced Endoplasmic Reticulum Stress Impairs Selective Autophagy at the Step of Autophagosome-Lysosome Fusion in Hepatocytes. Am J Pathol 186, 1861-73 27157992 Curated Info
21	Kageyama S, et al. (2014) Proteasome dysfunction activates autophagy and the keap1-nrf2 pathway. J Biol Chem 289, 24944-55 25049227 Curated Info
22	Ishimura R, Tanaka K, Komatsu M (2014) Dissection of the role of p62/Sqstm1 in activation of Nrf2 during xenophagy. FEBS Lett 588, 822-8 24492006 Curated Info
23	Ichimura Y, et al. (2013) Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. Mol Cell 51, 618-31 24011591 Curated Info