Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT880SE6)

• DOT Name: Myocyte-specific enhancer factor 2B (MEF2B)
• Synonyms: RSRFR2; Serum response factor-like protein 2
• Gene Name: MEF2B
• Related Disease:
  Adult lymphoma
  Advanced cancer
  B-cell lymphoma
  B-cell neoplasm
  Breast cancer
  Breast carcinoma
  Cerebellar ataxia
  Classic Hodgkin lymphoma
  Follicular lymphoma
  Lymphoma, non-Hodgkin, familial
  Mediastinal large B-cell lymphoma
  Non-hodgkin lymphoma
  Pediatric lymphoma
  Neoplasm
  Mantle cell lymphoma
  Marginal zone lymphoma
• UniProt ID: MEF2B_HUMAN
• PDB ID: 1N6J; 1TQE; 6BYY; 6BZ1; 6C9L; 6WC2; 6WC5
• Pfam ID: PF00319
• Sequence:
  MGRKKIQISRILDQRNRQVTFTKRKFGLMKKAYELSVLCDCEIALIIFNSANRLFQYAST
  DMDRVLLKYTEYSEPHESRTNTDILETLKRRGIGLDGPELEPDEGPEEPGEKFRRLAGEG
  GDPALPRPRLYPAAPAMPSPDVVYGALPPPGCDPSGLGEALPAQSRPSPFRPAAPKAGPP
  GLVHPLFSPSHLTSKTPPPLYLPTEGRRSDLPGGLAGPRGGLNTSRSLYSGLQNPCSTAT
  PGPPLGSFPFLPGGPPVGAEAWARRVPQPAAPPRRPPQSASSLSASLRPPGAPATFLRPS
  PIPCSSPGPWQSLCGLGPPCAGCPWPTAGPGRRSPGGTSPERSPGTARARGDPTSLQASS
  EKTQQ
• Function: Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific genes. Activates transcription via this element. May be involved in muscle-specific and/or growth factor-related transcription.
• Tissue Specificity: Expressed in skeletal and cardiac muscle and brain.
• KEGG Pathway:
  cGMP-PKG sig.ling pathway (hsa04022)
  Apelin sig.ling pathway (hsa04371)
• Reactome Pathway: Myogenesis (R-HSA-525793)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult lymphoma	DISK8IZR	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[2]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[3]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[6]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[4]
Follicular lymphoma	DISVEUR6	Strong	Biomarker	[4]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Genetic Variation	[2]
Mediastinal large B-cell lymphoma	DISAUA10	Strong	Biomarker	[7]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Genetic Variation	[2]
Pediatric lymphoma	DIS51BK2	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[8]
Mantle cell lymphoma	DISFREOV	Limited	Biomarker	[4]
Marginal zone lymphoma	DISLZ4AO	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Myocyte-specific enhancer factor 2B (MEF2B).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Myocyte-specific enhancer factor 2B (MEF2B).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Myocyte-specific enhancer factor 2B (MEF2B).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Myocyte-specific enhancer factor 2B (MEF2B).	[12]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Myocyte-specific enhancer factor 2B (MEF2B).	[13]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Myocyte-specific enhancer factor 2B (MEF2B).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Myocyte-specific enhancer factor 2B (MEF2B).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the expression of Myocyte-specific enhancer factor 2B (MEF2B).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Myocyte-specific enhancer factor 2B (MEF2B).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Myocyte-specific enhancer factor 2B (MEF2B).	[18]

References

• [1] MEF2B Instructs Germinal Center Development and Acts as an Oncogene in B Cell Lymphomagenesis.Cancer Cell. 2018 Sep 10;34(3):453-465.e9. doi: 10.1016/j.ccell.2018.08.006.
• [2] The Cancer Mutation D83V Induces an -Helix to -Strand Conformation Switch in MEF2B.J Mol Biol. 2018 Apr 13;430(8):1157-1172. doi: 10.1016/j.jmb.2018.02.012. Epub 2018 Feb 22.
• [3] MEF2B is a member of the BCL6 gene transcriptional complex and induces its expression in diffuse large B-cell lymphoma of the germinal center B-cell-like type.Lab Invest. 2019 Apr;99(4):539-550. doi: 10.1038/s41374-018-0152-2. Epub 2018 Nov 16.
• [4] Comparison of Myocyte Enhancer Factor 2B Versus Other Germinal Center-associated Antigens in the Differential Diagnosis of B-Cell Non-Hodgkin Lymphomas.Am J Surg Pathol. 2018 Mar;42(3):342-350. doi: 10.1097/PAS.0000000000001015.
• [5] A kinome-wide high-content siRNA screen identifies MEK5-ERK5 signaling as critical for breast cancer cell EMT and metastasis.Oncogene. 2018 Aug;37(31):4197-4213. doi: 10.1038/s41388-018-0270-8. Epub 2018 May 1.
• [6] Landscape of somatic mutations and clonal evolution in mantle cell lymphoma.Proc Natl Acad Sci U S A. 2013 Nov 5;110(45):18250-5. doi: 10.1073/pnas.1314608110. Epub 2013 Oct 21.
• [7] J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.Hum Pathol. 2017 Oct;68:47-53. doi: 10.1016/j.humpath.2017.08.015. Epub 2017 Aug 26.
• [8] MEF2 plays a significant role in the tumor inhibitory mechanism of encapsulated RENCA cells via EGF receptor signaling in target tumor cells.BMC Cancer. 2018 Dec 4;18(1):1217. doi: 10.1186/s12885-018-5128-5.
• [9] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [12] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [13] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [14] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] High-throughput data integration of RNA-miRNA-circRNA reveals novel insights into mechanisms of benzo[a]pyrene-induced carcinogenicity. Nucleic Acids Res. 2015 Mar 11;43(5):2525-34. doi: 10.1093/nar/gkv115. Epub 2015 Feb 17.
• [17] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.