Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL5ESAC)

DOT Name Transcription factor E4F1 (E4F1)
Synonyms EC 2.3.2.27; E4F transcription factor 1; Putative E3 ubiquitin-protein ligase E4F1; RING-type E3 ubiquitin transferase E4F1; Transcription factor E4F; p120E4F; p50E4F
Gene Name E4F1
Related Disease
Neoplasm ( )
Mitochondrial disease ( )
Pancytopenia ( )
UniProt ID
E4F1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.3.2.27
Pfam ID
PF00096 ; PF13912
Sequence
MEGAMAVRVTAAHTAEAQAEAGREAGEGAVAAVAAALAPSGFLGLPAPFSEEDEDDVHRC
GRCQAEFTALEDFVQHKIQKACQRAPPEALPATPATTALLGQEVVPAAPGPEEPITVAHI
VVEAASLAADISHASDLVGGGHIKEVIVAAEAELGDGEMAEAPGSPRQQGLGLAGEGEQA
QVKLLVNKDGRYVCALCHKTFKTGSILKAHMVTHSSRKDHECKLCGASFRTKGSLIRHHR
RHTDERPYKCSKCGKSFRESGALTRHLKSLTPCTEKIRFSVSKDVVVSKEDARAGSGAGA
AGLGTATSSVTGEPIETSPVIHLVTDAKGTVIHEVHVQMQELSLGMKALAPEPPVSQELP
CSSEGSRENLLHQAMQNSGIVLERAAGEEGALEPAPAAGSSPQPLAVAAPQLPVLEVQPL
ETQVASEASAVPRTHPCPQCSETFPTAATLEAHKRGHTGPRPFACAQCGKAFPKAYLLKK
HQEVHVRERRFRCGDCGKLYKTIAHVRGHRRVHSDERPYPCPKCGKRYKTKNAQQVHFRT
HLEEKPHVCQFCSRGFREKGSLVRHVRHHTGEKPFKCYKCGRGFAEHGTLNRHLRTKGGC
LLEVEELLVSEDSPAAATTVLTEDPHTVLVEFSSVVADTQEYIIEATADDAETSEATEII
EGTQTEVDSHIMKVVQQIVHQASAGHQIIVQNVTMDEETALGPEAAAADTITIATPESLT
EQVAMTLASAISEGTVLAARAGTSGTEQATVTMVSSEDIEILEHAGELVIASPEGQLEVQ
TVIV
Function
May function as a transcriptional repressor. May also function as a ubiquitin ligase mediating ubiquitination of chromatin-associated TP53. Functions in cell survival and proliferation through control of the cell cycle. Functions in the p53 and pRB tumor suppressor pathways and regulates the cyclin CCNA2 transcription.; Identified as a cellular target of the adenoviral oncoprotein E1A, it is required for both transcriptional activation and repression of viral genes.
Tissue Specificity Ubiquitously expressed.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neoplasm DISZKGEW Definitive Biomarker [1]
Mitochondrial disease DISKAHA3 Strong Biomarker [2]
Pancytopenia DISVKEHV Strong Genetic Variation [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Transcription factor E4F1 (E4F1). [4]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Transcription factor E4F1 (E4F1). [10]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Transcription factor E4F1 (E4F1). [5]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Transcription factor E4F1 (E4F1). [6]
Selenium DM25CGV Approved Selenium increases the expression of Transcription factor E4F1 (E4F1). [7]
Hydroquinone DM6AVR4 Approved Hydroquinone increases the expression of Transcription factor E4F1 (E4F1). [8]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of Transcription factor E4F1 (E4F1). [9]
ELLAGIC ACID DMX8BS5 Investigative ELLAGIC ACID increases the expression of Transcription factor E4F1 (E4F1). [9]
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⏷ Show the Full List of 6 Drug(s)

References

1 E4F1 deficiency results in oxidative stress-mediated cell death of leukemic cells.J Exp Med. 2011 Jul 4;208(7):1403-17. doi: 10.1084/jem.20101995. Epub 2011 Jun 27.
2 New genes and pathomechanisms in mitochondrial disorders unraveled by NGS technologies.Biochim Biophys Acta. 2016 Aug;1857(8):1326-1335. doi: 10.1016/j.bbabio.2016.02.022. Epub 2016 Mar 8.
3 E4F1 is a master regulator of CHK1-mediated functions.Cell Rep. 2015 Apr 14;11(2):210-9. doi: 10.1016/j.celrep.2015.03.019. Epub 2015 Apr 2.
4 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.
5 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
6 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.
7 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
8 E4F1 silencing inhibits the cell growth through cell-cycle arrest in malignant transformed cells induced by hydroquinone. J Biochem Mol Toxicol. 2019 Apr;33(4):e22269. doi: 10.1002/jbt.22269. Epub 2018 Dec 1.
9 Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002 Mar 1;70(15):1821-39.
10 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.