Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQFSQEE)

• DOT Name: Leucine zipper putative tumor suppressor 2 (LZTS2)
• Synonyms: hLZTS2; Protein LAPSER1
• Gene Name: LZTS2
• Related Disease:
  Advanced cancer
  Bladder cancer
  Carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Prostate neoplasm
  Laryngeal squamous cell carcinoma
  Prostate cancer
  Prostate carcinoma
  Nasopharyngeal carcinoma
• UniProt ID: LZTS2_HUMAN
• Pfam ID: PF06818
• Sequence:
  MAIVQTLPVPLEPAPEAATAPQAPVMGSVSSLISGRPCPGGPAPPRHHGPPGPTFFRQQD
  GLLRGGYEAQEPLCPAVPPRKAVPVTSFTYINEDFRTESPPSPSSDVEDAREQRAHNAHL
  RGPPPKLIPVSGKLEKNMEKILIRPTAFKPVLPKPRGAPSLPSFMGPRATGLSGSQGSLT
  QLFGGPASSSSSSSSSSAADKPLAFSGWASGCPSGTLSDSGRNSLSSLPTYSTGGAEPTT
  SSPGGHLPSHGSGRGALPGPARGVPTGPSHSDSGRSSSSKSTGSLGGRVAGGLLGSGTRA
  SPDSSSCGERSPPPPPPPPSDEALLHCVLEGKLRDREAELQQLRDSLDENEATMCQAYEE
  RQRHWQREREALREDCAAQAQRAQRAQQLLQLQVFQLQQEKRQLQDDFAQLLQEREQLER
  RCATLEREQRELGPRLEETKWEVCQKSGEISLLKQQLKESQAELVQKGSELVALRVALRE
  ARATLRVSEGRARGLQEAARARELELEACSQELQRHRQEAEQLREKAGQLDAEAAGLREP
  PVPPATADPFLLAESDEAKVQRAAAGVGGSLRAQVERLRVELQRERRRGEEQRDSFEGER
  LAWQAEKEQVIRYQKQLQHNYIQMYRRNRQLEQELQQLSLELEARELADLGLAEQAPCIC
  LEEITATEI
• Function: Negative regulator of katanin-mediated microtubule severing and release from the centrosome. Required for central spindle formation and the completion of cytokinesis. May negatively regulate axonal outgrowth by preventing the formation of microtubule bundles that are necessary for transport within the elongating axon. Negative regulator of the Wnt signaling pathway. Represses beta-catenin-mediated transcriptional activation by promoting the nuclear exclusion of beta-catenin.
• Tissue Specificity: Highly expressed in prostate and testis, and at slightly lower levels in spleen, thymus, uterus, small intestine and colon.
• KEGG Pathway: Wnt sig.ling pathway (hsa04310)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Bladder cancer	DISUHNM0	Strong	Biomarker	[2]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[3]
Lung cancer	DISCM4YA	Strong	Biomarker	[4]
Lung carcinoma	DISTR26C	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Posttranslational Modification	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[4]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[6]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Posttranslational Modification	[5]
Prostate cancer	DISF190Y	moderate	Altered Expression	[3]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[3]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[7]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Leucine zipper putative tumor suppressor 2 (LZTS2).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Leucine zipper putative tumor suppressor 2 (LZTS2).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Leucine zipper putative tumor suppressor 2 (LZTS2).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Leucine zipper putative tumor suppressor 2 (LZTS2).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Leucine zipper putative tumor suppressor 2 (LZTS2).	[12]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Leucine zipper putative tumor suppressor 2 (LZTS2).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Leucine zipper putative tumor suppressor 2 (LZTS2).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Leucine zipper putative tumor suppressor 2 (LZTS2).	[16]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Leucine zipper putative tumor suppressor 2 (LZTS2).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Leucine zipper putative tumor suppressor 2 (LZTS2).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Leucine zipper putative tumor suppressor 2 (LZTS2).	[18]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Leucine zipper putative tumor suppressor 2 (LZTS2).	[17]

References

• [1] LAPSER1 is a putative cytokinetic tumor suppressor that shows the same centrosome and midbody subcellular localization pattern as p80 katanin.FASEB J. 2007 Jul;21(9):2086-100. doi: 10.1096/fj.06-7254com. Epub 2007 Mar 9.
• [2] Deletion of leucine zipper tumor suppressor 2 (Lzts2) increases susceptibility to tumor development.J Biol Chem. 2013 Feb 8;288(6):3727-38. doi: 10.1074/jbc.M112.417568. Epub 2012 Dec 28.
• [3] LZTS2 and PTEN collaboratively regulate -catenin in prostatic tumorigenesis.PLoS One. 2017 Mar 21;12(3):e0174357. doi: 10.1371/journal.pone.0174357. eCollection 2017.
• [4] Leucine zipper tumor suppressor 2 inhibits cell proliferation and regulates Lef/Tcf-dependent transcription through Akt/GSK3 signaling pathway in lung cancer.J Histochem Cytochem. 2013 Sep;61(9):659-70. doi: 10.1369/0022155413495875. Epub 2013 Jun 12.
• [5] LZTS2 promoter hypermethylation: a potential biomarker for the diagnosis and prognosis of laryngeal squamous cell carcinoma.World J Surg Oncol. 2018 Mar 2;16(1):42. doi: 10.1186/s12957-018-1349-y.
• [6] LAPSER1: a novel candidate tumor suppressor gene from 10q24.3.Oncogene. 2001 Oct 11;20(46):6707-17. doi: 10.1038/sj.onc.1204866.
• [7] LZTS2 inhibits PI3K/AKT activation and radioresistance in nasopharyngeal carcinoma by interacting with p85.Cancer Lett. 2018 Apr 28;420:38-48. doi: 10.1016/j.canlet.2018.01.067. Epub 2018 Jan 31.
• [8] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [9] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [10] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [13] Malathion induced cancer-linked gene expression in human lymphocytes. Environ Res. 2020 Mar;182:109131. doi: 10.1016/j.envres.2020.109131. Epub 2020 Jan 10.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [16] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [17] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.