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Molecule Details

General Information of the Molecule
Name
Sequestosome-1 p62 (SQSTM1)
Synonyms
Ubiquitin-binding protein p62; Sequestosome-1; Phosphotyrosine-independent ligand for the Lck SH2 domain of 62kDa; Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa; OSIL; ORCA; EBIAP; EBI3-associated protein of 60 kDa
Gene Name
SQSTM1
Gene ID
8878
Sequence
MASLTVKAYLLGKEDAAREIRRFSFCCSPEPEAEAEAAAGPGPCERLLSRVAALFPALRP
GGFQAHYRDEDGDLVAFSSDEELTMAMSYVKDDIFRIYIKEKKECRRDHRPPCAQEAPRN
MVHPNVICDGCNGPVVGTRYKCSVCPDYDLCSVCEGKGLHRGHTKLAFPSPFGHLSEGFS
HSRWLRKVKHGHFGWPGWEMGPPGNWSPRPPRAGEARPGPTAESASGPSEDPSVNFLKNV
GESVAAALSPLGIEVDIDVEHGGKRSRLTPVSPESSSTEEKSSSQPSSCCSDPSKPGGNV
EGATQSLAEQMRKIALESEGRPEEQMESDNCSGGDDDWTHLSSKEVDPSTGELQSLQMPE
SEGPSSLDPSQEGPTGLKEAALYPHLPPEADPRLIESLSQMLSMGFSDEGGWLTRLLQTK
NYDIGAALDTIQYSKHPPPL
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Function
Autophagy receptor required for selective macroautophagy (aggrephagy). Functions as a bridge between polyubiquitinated cargo and autophagosomes. Interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family. Along with WDFY3, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with WDFY3, required to recruit ubiquitinated proteins to PML bodies in the nucleus. May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1. May play a role in titin/TTN downstream signaling in muscle cells. May regulate signaling cascades through ubiquitination. Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels. Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport. Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes. Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes.
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Uniprot ID
SQSTM_HUMAN
Pfam
PF00564 ; PF16577 ; PF00569
KEGG ID
hsa8878
TTD ID
T17367
A List of Drug Combination(s) Able to Regulate This Molecule
          Expression Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Expression of This Molecule [1]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 2 Down-regulating the Expression of This Molecule [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Gambogic acid   NP Info  + Chloroquine   Drug Info 
                    Structure +
                    Drug Combination 3 Down-regulating the Expression of This Molecule [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Ginsenoside Rg3   NP Info  + Endostar   Drug Info 
                    Structure +
                    Drug Combination 4 Down-regulating the Expression of This Molecule [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Vitamin D   NP Info  + Temozolomide   Drug Info 
                    Structure +
                    Drug Combination 5 Down-regulating the Expression of This Molecule [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 6 Down-regulating the Expression of This Molecule [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Everolimus   Drug Info 
                    Structure +
                    Drug Combination 7 Down-regulating the Expression of This Molecule [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Pterostilbene   NP Info  + Sorafenib   Drug Info 
                    Structure +
                    Drug Combination 8 Down-regulating the Expression of This Molecule [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Carnosic acid   NP Info  + Temozolomide   Drug Info 
                    Structure +
                 Up-regulation     Click to Show/Hide
                    Drug Combination 1 Up-regulating the Expression of This Molecule [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Epigallocatechin gallate   NP Info  + Gefitinib   Drug Info 
                    Structure +
                    Drug Combination 2 Up-regulating the Expression of This Molecule [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Deguelin   NP Info  + Doxorubicin   Drug Info 
                    Structure +
                    Drug Combination 3 Up-regulating the Expression of This Molecule [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Betulinic Acid   NP Info  + Erlotinib   Drug Info 
                    Structure +
                    Drug Combination 4 Up-regulating the Expression of This Molecule [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Honokiol   NP Info  + Chloroquine   Drug Info 
                    Structure +
                    Drug Combination 5 Up-regulating the Expression of This Molecule [14]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Androgen   Drug Info 
                    Structure +
                    Drug Combination 6 Up-regulating the Expression of This Molecule [15]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Chloroquine   Drug Info 
                    Structure +
                    Drug Combination 7 Up-regulating the Expression of This Molecule [16]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Celastrol   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 8 Up-regulating the Expression of This Molecule [17]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Genistein   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 9 Up-regulating the Expression of This Molecule [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Betulinic Acid   NP Info  + Gefitinib   Drug Info 
                    Structure +
                    Drug Combination 10 Up-regulating the Expression of This Molecule [18]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Gingerol   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 11 Up-regulating the Expression of This Molecule [19]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Thalidomide   Drug Info 
                    Structure +
                    Drug Combination 12 Up-regulating the Expression of This Molecule [20]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + Rapamycin   Drug Info 
                    Structure +
          Degradation Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Induction     Click to Show/Hide
                    Drug Combination 1 Inducting the Degradation of This Molecule [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Bortezomib   Drug Info 
                    Structure +
Natural Product(s) of This Target
1 Brusatol  NP Info  Investigative Brucea javanica
References
Reference 1 Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21(WAF1/CIP1) and C/EBPbeta expressions and suppressing NF-kappaB activation. Prostate. 2002 May 15;51(3):211-8.
Reference 2 Gambogic acid induces autophagy and combines synergistically with chloroquine to suppress pancreatic cancer by increasing the accumulation of reactive oxygen species. Cancer Cell Int. 2019 Jan 5;19:7.
Reference 3 Inhibiting effect of Endostar combined with ginsenoside Rg3 on breast cancer tumor growth in tumor-bearing mice. Asian Pac J Trop Med. 2016 Feb;9(2):180-3.
Reference 4 Autophagy enhancement contributes to the synergistic effect of vitamin D in temozolomide-based glioblastoma chemotherapy. Exp Ther Med. 2016 Jun;11(6):2153-2162.
Reference 5 Resveratrol Enhances Chemosensitivity in Mouse Melanoma Model Through Connexin 43 Upregulation. Environ Toxicol. 2015 Jul 8;30(8):877-86.
Reference 6 Arsenic trioxide synergizes with everolimus (Rad001) to induce cytotoxicity of ovarian cancer cells through increased autophagy and apoptosis. Endocr Relat Cancer. 2012 Sep 21;19(5):711-23.
Reference 7 Pterostilbene enhances sorafenib's anticancer effects on gastric adenocarcinoma. J Cell Mol Med. 2020 Nov;24(21):12525-12536.
Reference 8 Carnosic acid potentiates the anticancer effect of temozolomide by inducing apoptosis and autophagy in glioma. J Neurooncol. 2019 Jan;141(2):277-288.
Reference 9 Rationale and efficacy of proteasome inhibitor combined with arsenic trioxide in the treatment of acute promyelocytic leukemia. Leukemia. 2016 Nov;30(11):2169-2178.
Reference 10 Epigallocatechin gallate sensitizes CAL-27 human oral squamous cell carcinoma cells to the anti-metastatic effects of gefitinib (Iressa) via synergistic suppression of epidermal growth factor receptor and matrix metalloproteinase-2. Oncol Rep. 2012 Nov;28(5):1799-807.
Reference 11 Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin. Int J Mol Sci. 2017 Feb 10;18(2):370.
Reference 12 Effects and mechanisms of betulinic acid on improving EGFR TKI-resistance of lung cancer cells. Environ Toxicol. 2018 Nov;33(11):1153-1159.
Reference 13 Honokiol exhibits enhanced antitumor effects with chloroquine by inducing cell death and inhibiting autophagy in human non-small cell lung cancer cells. Oncol Rep. 2015 Sep;34(3):1289-300.
Reference 14 Arsenic trioxide enhances the radiation sensitivity of androgen-dependent and -independent human prostate cancer cells. PLoS One. 2012;7(2):e31579.
Reference 15 Chloroquine exerts antitumor effects on NB4 acute promyelocytic leukemia cells and functions synergistically with arsenic trioxide. Oncol Lett. 2018 Feb;15(2):2024-2030.
Reference 16 Autophagy flux inhibition mediated by celastrol sensitized lung cancer cells to TRAIL?induced apoptosis via regulation of mitochondrial transmembrane potential and reactive oxygen species. Mol Med Rep. 2019 Feb;19(2):984-993.
Reference 17 Genistein enhances TRAIL-induced apoptosis through inhibition of p38 MAPK signaling in human hepatocellular carcinoma Hep3B cells. Chem Biol Interact. 2009 Jul 15;180(2):143-50.
Reference 18 Inhibition of the autophagy flux by gingerol enhances TRAIL-induced tumor cell death. Oncol Rep. 2015 May;33(5):2331-6.
Reference 19 Inhibitory Effects of Arsenic Trioxide and Thalidomide on Angiogenesis and Vascular Endothelial Growth Factor Expression in Leukemia Cells. Asian Pac J Cancer Prev. 2018 Apr 27;19(4):1127-1134.
Reference 20 Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling. Cancer Lett. 2011 Feb 28;301(2):168-76.
Reference 21 Tamoxifen activates Nrf2-dependent SQSTM1 transcription to promote endometrial hyperplasia. Theranostics. 2017 Apr 10;7(7):1890-1900.
Cite NPCDR
Visitor Map
Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China