Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJYLJ02)

DOT Name mRNA decay activator protein ZFP36
Synonyms G0/G1 switch regulatory protein 24; Growth factor-inducible nuclear protein NUP475; Tristetraprolin; Zinc finger protein 36; Zfp-36
Gene Name ZFP36
UniProt ID
TTP_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4J8S
Pfam ID
PF00642
Sequence
MDLTAIYESLLSLSPDVPVPSDHGGTESSPGWGSSGPWSLSPSDSSPSGVTSRLPGRSTS
LVEGRSCGWVPPPPGFAPLAPRLGPELSPSPTSPTATSTTPSRYKTELCRTFSESGRCRY
GAKCQFAHGLGELRQANRHPKYKTELCHKFYLQGRCPYGSRCHFIHNPSEDLAAPGHPPV
LRQSISFSGLPSGRRTSPPPPGLAGPSLSSSSFSPSSSPPPPGDLPLSPSAFSAAPGTPL
ARRDPTPVCCPSCRRATPISVWGPLGGLVRTPSVQSLGSDPDEYASSGSSLGGSDSPVFE
AGVFAPPQPVAAPRRLPIFNRISVSE
Function
Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis. Acts as an 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery. Recruits deadenylase CNOT7 (and probably the CCR4-NOT complex) via association with CNOT1, and hence promotes ARE-mediated mRNA deadenylation. Functions also by recruiting components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs. Self regulates by destabilizing its own mRNA. Binds to 3'-UTR ARE of numerous mRNAs and of its own mRNA. Plays a role in anti-inflammatory responses; suppresses tumor necrosis factor (TNF)-alpha production by stimulating ARE-mediated TNF-alpha mRNA decay and several other inflammatory ARE-containing mRNAs in interferon (IFN)- and/or lipopolysaccharide (LPS)-induced macrophages. Also plays a role in the regulation of dendritic cell maturation at the post-transcriptional level, and hence operates as part of a negative feedback loop to limit the inflammatory response. Promotes ARE-mediated mRNA decay of hypoxia-inducible factor HIF1A mRNA during the response of endothelial cells to hypoxia. Positively regulates early adipogenesis of preadipocytes by promoting ARE-mediated mRNA decay of immediate early genes (IEGs). Negatively regulates hematopoietic/erythroid cell differentiation by promoting ARE-mediated mRNA decay of the transcription factor STAT5B mRNA. Plays a role in maintaining skeletal muscle satellite cell quiescence by promoting ARE-mediated mRNA decay of the myogenic determination factor MYOD1 mRNA. Associates also with and regulates the expression of non-ARE-containing target mRNAs at the post-transcriptional level, such as MHC class I mRNAs. Participates in association with argonaute RISC catalytic components in the ARE-mediated mRNA decay mechanism; assists microRNA (miRNA) targeting ARE-containing mRNAs. May also play a role in the regulation of cytoplasmic mRNA decapping; enhances decapping of ARE-containing RNAs, in vitro. Involved in the delivery of target ARE-mRNAs to processing bodies (PBs). In addition to its cytosolic mRNA-decay function, affects nuclear pre-mRNA processing. Negatively regulates nuclear poly(A)-binding protein PABPN1-stimulated polyadenylation activity on ARE-containing pre-mRNA during LPS-stimulated macrophages. Also involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion. Plays a role in the regulation of keratinocyte proliferation, differentiation and apoptosis. Plays a role as a tumor suppressor by inhibiting cell proliferation in breast cancer cells ; (Microbial infection) Negatively regulates HTLV-1 TAX-dependent transactivation of viral long terminal repeat (LTR) promoter.
Tissue Specificity
Expressed in both basal and suprabasal epidermal layers . Expressed in epidermal keratinocytes . Expressed strongly in mature dendritic cells . Expressed in immature dendritic cells (at protein level) .
KEGG Pathway
Human T-cell leukemia virus 1 infection (hsa05166 )
Kaposi sarcoma-associated herpesvirus infection (hsa05167 )
Reactome Pathway
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA (R-HSA-450513 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
37 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 mRNA decay activator protein ZFP36. [1]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of mRNA decay activator protein ZFP36. [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of mRNA decay activator protein ZFP36. [3]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of mRNA decay activator protein ZFP36. [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of mRNA decay activator protein ZFP36. [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of mRNA decay activator protein ZFP36. [6]
Estradiol DMUNTE3 Approved Estradiol increases the expression of mRNA decay activator protein ZFP36. [7]
Quercetin DM3NC4M Approved Quercetin increases the expression of mRNA decay activator protein ZFP36. [8]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of mRNA decay activator protein ZFP36. [9]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of mRNA decay activator protein ZFP36. [10]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of mRNA decay activator protein ZFP36. [11]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of mRNA decay activator protein ZFP36. [12]
Testosterone DM7HUNW Approved Testosterone increases the expression of mRNA decay activator protein ZFP36. [13]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of mRNA decay activator protein ZFP36. [14]
Marinol DM70IK5 Approved Marinol increases the expression of mRNA decay activator protein ZFP36. [15]
Progesterone DMUY35B Approved Progesterone increases the expression of mRNA decay activator protein ZFP36. [16]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of mRNA decay activator protein ZFP36. [17]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of mRNA decay activator protein ZFP36. [18]
Cannabidiol DM0659E Approved Cannabidiol increases the expression of mRNA decay activator protein ZFP36. [19]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of mRNA decay activator protein ZFP36. [20]
Nicotine DMWX5CO Approved Nicotine increases the activity of mRNA decay activator protein ZFP36. [21]
Hydrocortisone DMGEMB7 Approved Hydrocortisone increases the expression of mRNA decay activator protein ZFP36. [22]
Gentamicin DMKINJO Approved Gentamicin increases the expression of mRNA decay activator protein ZFP36. [6]
Tobramycin DMUI0CH Approved Tobramycin increases the expression of mRNA decay activator protein ZFP36. [6]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of mRNA decay activator protein ZFP36. [23]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of mRNA decay activator protein ZFP36. [24]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of mRNA decay activator protein ZFP36. [25]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of mRNA decay activator protein ZFP36. [26]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of mRNA decay activator protein ZFP36. [27]
Afimoxifene DMFORDT Phase 2 Afimoxifene increases the expression of mRNA decay activator protein ZFP36. [7]
phorbol 12-myristate 13-acetate DMJWD62 Phase 2 phorbol 12-myristate 13-acetate increases the expression of mRNA decay activator protein ZFP36. [28]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of mRNA decay activator protein ZFP36. [29]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of mRNA decay activator protein ZFP36. [30]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of mRNA decay activator protein ZFP36. [31]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of mRNA decay activator protein ZFP36. [33]
chloropicrin DMSGBQA Investigative chloropicrin increases the expression of mRNA decay activator protein ZFP36. [34]
4-hydroxy-2-nonenal DM2LJFZ Investigative 4-hydroxy-2-nonenal decreases the expression of mRNA decay activator protein ZFP36. [35]
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⏷ Show the Full List of 37 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of mRNA decay activator protein ZFP36. [32]
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