Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7DU7WN)

• DOT Name: CBP80/20-dependent translation initiation factor (CTIF)
• Gene Name: CTIF
• Related Disease:
  Parkinson disease
  Rheumatoid arthritis
  Schizophrenia
• UniProt ID: CTIF_HUMAN
• Pfam ID: PF02854
• Sequence:
  MENSSAASASSEAGSSRSQEIEELERFIDSYVLEYQVQGLLADKTEGDGESERTQSHISQ
  WTADCSEPLDSSCSFSRGRAPPQQNGSKDNSLDMLGTDIWAANTFDSFSGATWDLQPEKL
  DFTQFHRKVRHTPKQPLPHIDREGCGKGKLEDGDGINLNDIEKVLPAWQGYHPMPHEVEI
  AHTKKLFRRRRNDRRRQQRPPGGNKPQQHGDHQPGSAKHNRDHQKSYQGGSAPHPSGRPT
  HHGYSQNRRWHHGNMKHPPGDKGEAGAHRNAKETMTIENPKLEDTAGDTGHSSLEAPRSP
  DTLAPVASERLPPQQSGGPEVETKRKDSILPERIGERPKITLLQSSKDRLRRRLKEKDEV
  AVETTTPQQNKMDKLIEILNSMRNNSSDVDTKLTTFMEEAQNSTNSEEMLGEIVRTIYQK
  AVSDRSFAFTAAKLCDKMALFMVEGTKFRSLLLNMLQKDFTVREELQQQDVERWLGFITF
  LCEVFGTMRSSTGEPFRVLVCPIYTCLRELLQSQDVKEDAVLCCSMELQSTGRLLEEQLP
  EMMTELLASARDKMLCPSESMLTRSLLLEVIELHANSWNPLTPPITQYYNRTIQKLTA
• Function: Specifically required for the pioneer round of mRNA translation mediated by the cap-binding complex (CBC), that takes place during or right after mRNA export via the nuclear pore complex (NPC). Acts via its interaction with the NCBP1/CBP80 component of the CBC complex and recruits the 40S small subunit of the ribosome via eIF3. In contrast, it is not involved in steady state translation, that takes place when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. Also required for nonsense-mediated mRNA decay (NMD), the pioneer round of mRNA translation mediated by the cap-binding complex playing a central role in nonsense-mediated mRNA decay (NMD).
• Tissue Specificity: Widely 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
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[1]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of CBP80/20-dependent translation initiation factor (CTIF).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of CBP80/20-dependent translation initiation factor (CTIF).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CBP80/20-dependent translation initiation factor (CTIF).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of CBP80/20-dependent translation initiation factor (CTIF).	[7]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of CBP80/20-dependent translation initiation factor (CTIF).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of CBP80/20-dependent translation initiation factor (CTIF).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of CBP80/20-dependent translation initiation factor (CTIF).	[10]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of CBP80/20-dependent translation initiation factor (CTIF).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of CBP80/20-dependent translation initiation factor (CTIF).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of CBP80/20-dependent translation initiation factor (CTIF).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of CBP80/20-dependent translation initiation factor (CTIF).	[13]

References

• [1] Genome-wide genotyping in Parkinson's disease and neurologically normal controls: first stage analysis and public release of data.Lancet Neurol. 2006 Nov;5(11):911-6. doi: 10.1016/S1474-4422(06)70578-6.
• [2] REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.Nat Genet. 2009 Jul;41(7):820-3. doi: 10.1038/ng.395. Epub 2009 Jun 7.
• [3] Genome-wide association study identifies five new schizophrenia loci.Nat Genet. 2011 Sep 18;43(10):969-76. doi: 10.1038/ng.940.
• [4] 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.
• [5] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [9] 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.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] 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.