Affinage

ZFP36

mRNA decay activator protein ZFP36 · UniProt P26651

Length
326 aa
Mass
34.0 kDa
Annotated
2026-06-11
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ZFP36 (TTP/TIS11) is a CCCH tandem zinc-finger RNA-binding protein that acts as a master post-transcriptional repressor, binding AU-rich elements in target mRNA 3'-UTRs and coding sequences to drive their decay and translational silencing across immune, metabolic, vascular, and oncogenic programs (PMID:24401661, PMID:12324455, PMID:29848443). Each of its two Cys3His repeats coordinates a single zinc ion in tetrahedral geometry, and even one zinc-loaded domain confers selective binding to the UUAUUUAUU/UUUAUUU consensus, discriminating against sequences lacking the central adenine or flanking uridines (PMID:8943007, PMID:12705825, PMID:12324455); iron can substitute for zinc while preserving high-affinity, sequence-selective RNA binding (PMID:17087518). Originally identified as a primary response gene induced by tumor-promoter and serum stimulation via EGR-1/AP2/Sp1 promoter and intronic Sp1 elements (PMID:2915901, PMID:7559666, PMID:9417109), ZFP36 is wired into stimulus-coupled signaling: it is transcriptionally activated by ISGF3 (IFNβ), AngII/PARP1, and other inputs, and its repressive activity is switched off by p38-MK2-mediated phosphorylation that stabilizes ARE-containing cytokine mRNAs such as TNF, IL-6, and IL-8 (PMID:39117638, PMID:39589932, PMID:39046234). Genome-wide CLIP defined its in vivo AU-rich binding landscape, overlapping that of ELAVL1, and confirmed it as a direct decay factor for immune and cancer transcripts (PMID:24401661). Through this activity ZFP36 represses a broad target set—cytokines and inflammasome components (IL-27, NLRP3, TNF), signaling and metabolic regulators (RGS2, NOX4, Eno2, SIK1, RNF128, CREBBP, Jag1), cell-cycle and oncogenic drivers (CDK6, E2F1, PRC1, BARX1, CEMIP), and ferroptosis modulators (Ythdc2, ATG16L1, VDR)—placing it at control points in inflammation resolution, vascular tone, angiogenesis, adipocyte homeostasis, and tumor suppression (PMID:39589932, PMID:38157296, PMID:36111167, PMID:37587140, PMID:39761791, PMID:40000392). ZFP36 shuttles between nucleus and cytoplasm via a ZnF-region NLS and CRM1-dependent NES, partitions into stress granules through its tandem zinc fingers, and is itself controlled by rapid ubiquitin-independent proteasomal turnover driven by its disordered termini (blocked by phosphorylation) as well as FBXW7-directed degradation of an SFSGLPS degron (PMID:12054509, PMID:15652343, PMID:25246635, PMID:31679460). Beyond mRNA decay, ZFP36 associates with RIG-I and promotes its K63-linked polyubiquitination to enhance antiviral IFN-β signaling (PMID:37565597).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1991 Medium

    Establishing that ZFP36 belongs to a conserved family defined by tandem CCCH zinc fingers framed it as a putative nucleic-acid-binding protein rather than a featureless immediate-early product.

    Evidence cDNA cloning and cross-family sequence comparison identifying the YKTELC CCCH repeat shared with TIS11b/TIS11d

    PMID:1996120

    Open questions at the time
    • Domain identity did not establish a ligand or biochemical activity
    • No metal coordination or RNA-binding data
  2. 1996 High

    Determining that each Cys3His repeat coordinates one zinc ion in tetrahedral geometry provided the structural basis for how these fingers fold and function.

    Evidence Co2+ spectroscopy and NMR on synthetic ZFP36 zinc-finger peptides

    PMID:8943007

    Open questions at the time
    • Did not show what the folded finger binds
    • Used isolated peptides, not full-length protein
  3. 2003 High

    Defining the RNA target sequence and demonstrating selective high-affinity binding established ZFP36 as a sequence-specific AU-rich element reader.

    Evidence SELEX and RNA EMSA with recombinant protein (UUAUUUAUU consensus) plus quantitative fluorescence binding by a single zinc-loaded domain (UUUAUUU, ~5 µM, discriminating against non-canonical sequences)

    PMID:12324455 PMID:12705825

    Open questions at the time
    • In vitro binding did not establish in vivo target repertoire
    • Did not connect binding to mRNA fate
  4. 2006 Medium

    Showing iron can replace zinc in the two-domain protein while retaining nanomolar, sequence-selective RNA binding addressed which metal cofactor supports activity.

    Evidence Metal-ion titration and fluorescence RNA-binding assays with Fe2+/Fe3+-reconstituted recombinant TTP-2D

    PMID:17087518

    Open questions at the time
    • Physiological relevance of iron occupancy in cells not demonstrated
    • Single lab in vitro reconstitution
  5. 2004 Medium

    Mapping nucleocytoplasmic shuttling signals and stress-granule recruitment to the zinc-finger region established where ZFP36 acts and how its localization is controlled.

    Evidence GFP fusions, deletion/point mutagenesis, leptomycin B (CRM1 dependence), and heat-shock co-localization with stress-granule markers; later identification of a cryptic Transportin PY-NLS overlapping ZnF2

    PMID:12054509 PMID:15652343 PMID:23951221

    Open questions at the time
    • Functional consequence of nuclear pool not defined
    • Stress-granule role in target regulation not quantified
  6. 2014 High

    Genome-wide CLIP coupled to knockout mRNA half-life analysis transformed ZFP36 from a TNF-ARE binder into a defined global decay factor with a measurable in vivo target set.

    Evidence HITS-CLIP in human cells and ZFP36-KO mouse mRNA stability analysis, with comparison to ELAVL1 binding overlap

    PMID:24401661

    Open questions at the time
    • Did not resolve the deadenylase/decay machinery recruited
    • Binding-decay coupling varied by transcript
  7. 2014 Medium

    Defining ZFP36 turnover as ubiquitin-independent proteasomal degradation gated by phosphorylation, alongside FBXW7-directed degron recognition, explained how the repressor's own abundance is dynamically controlled.

    Evidence In vitro and cell-based proteasome/degradation assays with phosphorylation manipulation; FBXW7 SFSGLPS degron identification with in vivo overexpression

    PMID:25246635 PMID:31679460

    Open questions at the time
    • Relative contribution of ubiquitin-independent vs FBXW7 routes in vivo unclear
    • Kinases setting the degradation-protective phosphostate not fully mapped
  8. 2018 High

    Linking ZFP36 binding to both transcript abundance and translation in primary T cells with an in vivo infection phenotype established it as a brake on immune activation kinetics, not solely a decay enzyme.

    Evidence HITS-CLIP plus ribosome profiling and conditional Zfp36 knockout in acute viral infection in mice

    PMID:29848443

    Open questions at the time
    • Mechanism of translational (vs decay) repression not separated
    • Coding-sequence ARE function not biochemically defined
  9. 2024 Medium

    Reconstructing the upstream signaling that drives and inactivates ZFP36 connected its expression and activity to defined kinase and transcription-factor circuits across inflammation and necroptosis.

    Evidence ISGF3/IFNβ and MKK3-p38-MK2 manipulation with cytokine mRNA stability readouts; dsRNA/p38-MK2 phosphorylation linked to ARE-mRNA stabilization and reversed pharmacologically

    PMID:26546680 PMID:39046234 PMID:39117638

    Open questions at the time
    • Phosphosite-resolved mechanism of activity loss not structurally defined here
    • Feedback via DUSP1 quantified only in select cell types
  10. 2025 High

    A series of tissue-specific knockout and target-decay studies established ZFP36 as a physiological regulator of vascular tone, angiogenesis, adipocyte homeostasis, and tumor suppression through distinct 3'-UTR targets.

    Evidence Cell-type-specific Zfp36 knockouts with genetic/pharmacological rescue defining RGS2 (VSMC/hypertension), Jag1 (endothelial angiogenesis), RNF128 (adipose obesity), and oncogenic targets CDK6/E2F1/BARX1/PRC1/CEMIP/Ythdc2

    PMID:36111167 PMID:38157296 PMID:39589932 PMID:39761791

    Open questions at the time
    • Target hierarchy within each tissue not fully resolved
    • Many oncogenic targets rest on single-lab RIP/luciferase evidence
  11. 2023 Medium

    Identifying a decay-independent role in which ZFP36 promotes K63-linked polyubiquitination of RIG-I revealed an unexpected positive function in antiviral signaling.

    Evidence Co-IP, RIG-I ubiquitination-site mutagenesis, and ZFP36 zinc-finger mutant (C118S/C162S) in SeV infection

    PMID:37565597

    Open questions at the time
    • Whether ZFP36 acts as or recruits the relevant E3 is not defined
    • Single Co-IP-based mechanism without reconstitution

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ZFP36 mechanistically recruits the deadenylation/decay machinery and how phosphorylation, localization, and the decay-independent ubiquitin-promoting activity are integrated on a single transcript remain unresolved.
  • No structural model of ZFP36 on the decay machinery in the corpus
  • Mechanism by which ZFP36 promotes RIG-I ubiquitination undefined
  • Integration of nuclear pool and stress-granule partitioning with target decay unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0140098 catalytic activity, acting on RNA 4
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
ELAVL1FBXW7RIG-I

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 TIS11 (ZFP36) is a primary response gene rapidly and transiently induced in Swiss 3T3 cells by the tumor promoter TPA; cDNA sequence and deduced amino acid sequence were determined. cDNA cloning and sequencing Oncogene Low 2915901
1991 TIS11/ZFP36 protein contains two tandemly repeated CCCH-type Cys3His zinc-finger motifs (YKTELC repeat) that are highly conserved across a gene family including TIS11b and TIS11d. cDNA cloning, sequence comparison Molecular and cellular biology Medium 1996120
1991 IL-6 signal transduction in B-cell hybridoma activates TIS11 gene transcription through a novel protein kinase cascade requiring tyrosine kinase activity and an H7-sensitive kinase, independently of cycloheximide-sensitive protein synthesis. Pharmacological inhibition (cycloheximide, H7), tyrosine phosphorylation assays, primary response gene induction Molecular and cellular biology Medium 1705005
1995 The Zfp-36 promoter requires 77 bp 5' of the transcription start site for full serum inducibility; cis-acting elements for EGR-1, AP2, Sp1, and a novel TPE1 palindrome each contribute to serum-induced transcription. Promoter deletion analysis, gel mobility shift assay (EMSA), reporter gene assay The Journal of biological chemistry Medium 7559666
1996 The Nup475/ZFP36 Cys3His repeats each bind one equivalent of zinc (or cobalt) with tetrahedral coordination; NMR structural data indicate the zinc ion is coordinated by conserved cysteines and histidine, with the conserved YKTEL motif forming a parallel sheet-like structure. Metal-binding titration (Co2+ spectroscopy), NMR spectroscopy, synthetic peptides Proceedings of the National Academy of Sciences of the United States of America High 8943007
1998 Full serum-induced expression of Zfp-36 requires both promoter elements and an intronic element; a Sp1-binding sequence (bp 618-626) within the intron contributes ~70% of serum-induced expression. Intron replacement/deletion analysis, site-directed mutagenesis of Sp1 binding site, reporter gene assays The Journal of biological chemistry Medium 9417109
2000 TIS11/ZFP36 functions as a positive transcriptional activator when fused to a GAL4 DNA-binding domain; the N-terminal 101 amino acid region contains the major transactivation domain, and PMA negatively regulates this activity via protein kinase C/MAP kinase cascade. GAL4 fusion transactivation assay, deletion mutagenesis, pharmacological inhibition (calphostin C, PD98059) Biochemical and biophysical research communications Medium 10913371
2000 Continuous expression of TTP/ZFP36 at physiological levels causes apoptotic cell death dependent on the zinc finger domains; TTP but not TIS11b or TIS11d sensitizes cells to TNF-alpha-induced apoptosis. Stable transfection, apoptosis assays, zinc finger domain mutants Oncogene Medium 10763822
2002 Recombinant Nup475/ZFP36 protein binds the TNF AU-rich element via SELEX-determined optimal sequence UUAUUUAUU; zinc excess inhibits binding; the protein also shows weaker binding to poly(A) sequences. RNA gel shift (EMSA), RNA SELEX, site-directed mutagenesis of TNF ARE, recombinant protein from E. coli The Journal of biological chemistry High 12324455
2002 TIS11/ZFP36 contains a functional nuclear localization signal (NLS) in the tandem zinc-finger region (requiring Arg127 and Arg131) and a CRM1-dependent Leu-rich nuclear export signal (NES) in the N-terminal region, enabling nucleocytoplasmic shuttling. GFP fusion constructs, leptomycin B treatment, deletion analysis, site-directed mutagenesis Biochemical and biophysical research communications Medium 12054509
2003 A single CCCH zinc-binding domain of Nup475/ZFP36 is sufficient for selective RNA binding; the zinc(II)-complexed first domain binds UUUAUUU with ~5 µM affinity and discriminates against sequences lacking the central A or flanking U residues. Fluorescence-based binding assay with synthetic peptide, metal ion binding characterization Biochemistry High 12705825
2004 TIS11/ZFP36 is recruited to stress granules (SGs) upon heat shock; recruitment requires the tandem zinc-finger domain, with specific residues Tyr105/Tyr113, Gly109/Gly114, Phe119 and zinc-chelating Cys residues in both fingers being critical. GFP fusion constructs, deletion analysis, site-directed mutagenesis, heat shock treatment, co-localization with SG markers Experimental cell research Medium 15652343
2006 Iron (Fe2+ and Fe3+) can substitute for zinc in the TTP-2D (ZFP36 two-domain) protein; iron-substituted TTP-2D binds the canonical UUUAUUUAUUU RNA sequence with nanomolar affinity and retains selectivity for adenine-containing sequences. Metal ion titration, fluorescence-based RNA binding assay, Fe2+/Fe3+ reconstitution of recombinant protein Biochemistry Medium 17087518
2013 A cryptic Transportin-dependent PY-NLS overlapping the second zinc finger (ZnF2) is conserved across TIS11/ZFP36 family; mutations disrupting ZnF2 zinc coordination unmask this NLS and promote nuclear import; nuclear export in Drosophila dTIS11 is CRM1-dependent via a divergent NES. Deletion mutagenesis, zinc finger mutation, nuclear import/export assays, leptomycin B treatment, Drosophila and mammalian cell systems PloS one Medium 23951221
2014 ZFP36 globally binds AU-rich sequences in vivo; CLIP-seq defined in vivo binding preferences in human embryonic kidney cells; ZFP36 degrades target transcripts through specific AU-rich sequences representing a subset of U-rich sequences; targets include immune function and cancer transcripts; ZFP36 and ELAVL1 share overlapping binding sites in 1,313 genes but with differential relative preferences. HITS-CLIP (cross-linking and immunoprecipitation), mRNA half-life analysis in ZFP36 knockout mouse cells, partial correlation analysis Genome biology High 24401661
2014 Rapid proteasomal degradation of ZFP36/TTP is ubiquitin-independent and driven by intrinsically disordered N- and C-terminal domains; phosphorylation inhibits proteasomal degradation of TTP in vitro. Proteasome inhibitor assays, ubiquitin-independent degradation assays, in vitro degradation with phosphorylation manipulation, Drosophila dTIS11 and mammalian TTP Molecular and cellular biology Medium 25246635
2015 ZFP36 exerts negative feed-forward control of TNF mRNA expression via ARE-mediated mRNA degradation; DUSP1-dependent negative feedback on MAPKs reduces ZFP36 expression, limiting this feed-forward control; dexamethasone represses TNF independently of ZFP36. siRNA silencing of DUSP1 and ZFP36, DUSP1 overexpression, MAPK inhibition, TNF mRNA stability assays in primary human bronchial epithelial cells and A549 cells The Journal of biological chemistry Medium 26546680
2015 ZFP36 promotes assembly of the Ripoptosome death complex by depleting XIAP and cIAP2 ubiquitin ligases (via destabilizing their mRNAs), leading to RIP1 stabilization, association of RIP1 with caspase-8 and FADD, and RIP1-dependent cell death/necroptosis. Co-immunoprecipitation, size exclusion chromatography, shRNA lentivectors, cell death assays in glioma neural stem cells BMC cancer Medium 25939870
2018 ZFP36 represses mRNA target abundance and translation in T cells, including through novel AU-rich sites in coding sequences; ZFP36 regulates early T-cell activation kinetics by attenuating activation marker expression, limiting expansion, and promoting apoptosis; loss of ZFP36 in vivo accelerates T cell responses to acute viral infection. HITS-CLIP in mouse T cells, ribosome profiling, transcriptome analysis, in vivo viral infection model with ZFP36 conditional knockout eLife High 29848443
2019 ZFP36/TTP promotes ATG16L1 mRNA decay by binding AU-rich elements in its 3'-UTR; internal mutation of the ARE region abrogates ZFP36-mediated ATG16L1 mRNA instability; FBXW7 ubiquitin ligase degrades ZFP36 protein by recognizing a SFSGLPS motif, linking ZFP36 to ferroptosis resistance through autophagy inhibition. ARE mutagenesis, mRNA decay assays, plasmid overexpression, FBXW7 recognition motif identification, in vivo HSC-specific Zfp36 overexpression mouse model Autophagy Medium 31679460
2021 ZFP36 directly binds AU-rich elements in the NOX4 mRNA 3'-UTR to inhibit NOX4 expression, thereby suppressing NOX4-mediated DRP1 activation and mitochondrial fragmentation in neurons under OGD/R conditions. RNA immunoprecipitation (RIP), 3'-UTR binding assay, siRNA knockdown, ZFP36 overexpression, NOX4 inhibitor experiments Brain research bulletin Medium 34896479
2021 ZFP36 directly binds ARE sequences in the CREBBP mRNA 3'-UTR to promote its degradation, as confirmed by pull-down and RIP assays; ZFP36 deficiency upregulates CREBBP and enhances I/R-induced lung injury via CREBBP/p53/p21/Bax pathway. RIP assay, pull-down assay, in silico prediction, Western blot, in vivo ZFP36 knockdown mouse model Cell death & disease Medium 34238924
2020 ZFP36 binds AU-rich elements in the PRC1 mRNA 3'-UTR to downregulate PRC1 expression, suppressing HCC tumor growth and increasing 5-Fu sensitivity, as demonstrated by luciferase reporter and RIP assays. Luciferase reporter assay, RIP assay, ZFP36 overexpression, xenograft mouse model Frontiers in molecular biosciences Medium 32766276
2023 ZFP36 directly promotes mRNA decay of Enolase 2 (Eno2), altering Eno2 protein expression and enzymatic activity; ZFP36/L1/L2 family proteins are key drivers of metabolic regulation downstream of acute growth factor signaling, with ZFP36 binding catalogued against metabolic enzyme and nutrient transporter mRNAs. CLIP-seq, mRNA stability assays, Eno2 enzymatic activity measurement, VEGF-stimulated retinal angiogenesis model Cell reports Medium 37086408
2023 Jag1 mRNA is a direct target of ZFP36-mediated decay; VEGF induces ZFP36 in endothelial cells creating a feedforward loop that suppresses Jag1 to enable adequate Notch signaling; endothelial Zfp36 knockout mice show mispatterned JAG1 and increased tip cell numbers, rescued by Jag1 haploinsufficiency. ZFP36 CLIP, mRNA decay assays, endothelial-specific Zfp36 knockout mice, retinal vascular plexus imaging, Jag1 haploinsufficiency rescue Cell reports High 38157296
2023 ZFP36 associates with RIG-I and promotes K63-linked polyubiquitination of RIG-I at K154/K164/K172, facilitating RIG-I activation and IFN-β production during viral infection; a ZFP36 zinc-finger mutant (C118S/C162S) fails to promote RIG-I ubiquitination. Co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis of RIG-I ubiquitination sites, ZFP36 zinc-finger domain mutagenesis, SeV infection model Journal of cellular physiology Medium 37565597
2024 ZFP36 binds the 3'-UTR of RGS2 mRNA and promotes its degradation, thereby regulating GPCR-mediated intracellular calcium increases in vascular smooth muscle cells; VSMC-specific ZFP36 deletion reduces vessel contractility, blood pressure, and attenuates AngII-induced hypertension in mice; AngII activates ZFP36 transcription via PARP1. mRNA stability assays, VSMC-specific ZFP36 knockout mice, blood pressure measurement, calcium signaling assays, AAV-mediated knockdown in spontaneously hypertensive rats, PARP1 inhibitor experiments Advanced science High 39589932
2024 ZFP36 binds to the 3'-UTR of CREBBP/NLRP3 mRNAs to promote their decay; ZFP36 directly targets NLRP3 mRNA for degradation in fibroblasts, reducing inflammasome activation; ZFP36 gene undergoes promoter methylation in psoriatic fibroblasts reducing its expression. RIP assay, mRNA stability assay, ZFP36 restoration experiments, promoter methylation analysis, NLRP3 inflammasome activity assay Frontiers in medicine Medium 33585499
2024 IFNβ-induced ISGF3 transcription factor complex drives ZFP36 expression during necroptosis, and ZFP36 then post-transcriptionally degrades mRNAs of inflammatory cytokines (IL-6, IL-8, DUSP1, PTGS2, TNFAIP3) through ARE recognition; the MKK3-p38-MK2 axis regulates ZFP36 expression upstream. Transcriptomics, ISGF3 and MK2/MKK3 overexpression/knockdown, mRNA stability assays, ZFP36 knockdown validation, coronavirus infection models Cell death & disease Medium 39117638
2024 dsRNA/poly(I:C) activates p38 MAPK-MK2 signaling to phosphorylate ZFP36/TTP, inactivating it and stabilizing AU-rich cytokine mRNAs (TNF, IL-6, COX-2, IL-8); hydroxychloroquine reduces ZFP36 phosphorylation by suppressing p38/MK2, thereby reducing phosphorylated TTP abundance and destabilizing these inflammatory mRNAs. p38/MK2 phosphorylation assays, mRNA stability assays, hydroxychloroquine treatment, THP-1 and primary blood monocytes Immunology Medium 39046234
2025 Adipose ZFP36 represses RNF128 mRNA stability and translation; loss of ZFP36 in adipose tissue increases RNF128, which negatively regulates Sirt1, promoting adipocyte hypertrophy and obesity; adipose-specific ZFP36 knockout mice show decreased PLIN1, ATGL, and HSL expression and increased susceptibility to diet-induced obesity. Adipose-specific ZFP36 knockout mice, gene array assay, mRNA stability assay, in vivo metabolic phenotyping Metabolism: clinical and experimental Medium 39761791
2025 ZFP36 binds to the 3'-UTR of Ythdc2 mRNA to promote its degradation; loss of this suppression allows Ythdc2 to degrade SLC7A11 mRNA, reducing glutathione and promoting ferroptosis and cardiac hypertrophy; Ythdc2 overexpression reverses ZFP36-mediated protection. 3'-UTR binding assays, Ythdc2/SLC7A11 mRNA stability measurements, ZFP36 overexpression/knockdown in cardiomyocytes, transverse aortic constriction mouse model, epistasis rescue experiments Clinical and translational medicine Medium 40000392
2025 Smooth muscle ZFP36 binds CEMIP mRNA and promotes its degradation, reducing CEMIP protein and limiting VSMC proliferation and migration; smooth muscle-specific Zfp36 knockout accelerates neointimal hyperplasia; PDGF-BB downregulates ZFP36 in VSMCs via KLF4 binding to the Zfp36 promoter. Smooth muscle-specific ZFP36 knockout mice, carotid artery ligation model, mRNA stability assay for CEMIP, Cemip knockdown rescue, KLF4 promoter binding analysis Acta pharmacologica Sinica Medium 39890944
2021 ZFP36 directly binds AU-rich elements in the VDR mRNA 3'-UTR to promote its degradation; mutation of key amino acids in ZFP36 abolishes this mRNA binding; ZFP36-mediated VDR mRNA decay promotes cell death under inflammatory conditions. RNA affinity chromatography, ZFP36 key amino acid mutagenesis, mRNA decay assay, luciferase reporter (3'UTR ARE assay), Co-immunoprecipitation Cell communication and signaling Medium 34380509
2023 ZFP36 binds the 3'-UTR of BARX1 mRNA and mediates its destabilization; loss of ZFP36 leads to BARX1 upregulation, which transactivates oncogenes promoting NSCLC proliferation, migration, and invasion. ZFP36-BARX1 mRNA 3'UTR binding assays, mRNA stability assays, ZFP36/BARX1 knockdown/overexpression, NSCLC xenograft mouse model Cell death & disease Medium 37587140
2024 ZFP36 promotes E2F1 mRNA degradation by binding AREs in the E2F1 3'-UTR; loss of this suppression allows E2F1 to transactivate ATF4, collectively promoting malignant progression and suppressing ferroptosis in osteosarcoma. RIP assay, 3'-UTR ARE binding assay, E2F1/ATF4 promoter transactivation assays, ZFP36/E2F1/ATF4 overexpression/knockdown, in vivo xenograft Journal of pharmaceutical analysis Medium 41050116
2024 ZFP36 binds to SIK1 mRNA (confirmed by RIP) to promote its degradation; in high-glucose conditions, upregulated ZFP36 suppresses SIK1, promoting gluconeogenesis; DUSP1 overexpression downregulates ZFP36, relieving SIK1 suppression and inhibiting gluconeogenesis. RNA binding protein immunoprecipitation (RIP), ZFP36 overexpression/knockdown, DUSP1 overexpression, gluconeogenesis assays The Kaohsiung journal of medical sciences Low 36524461
2021 Macrophage-expressed ZFP36 promotes degradation of IL-27 p28 mRNA (confirmed by siRNA-mediated ZFP36 silencing leading to impaired IL-27 mRNA degradation); macrophage-specific Zfp36 conditional knockout leads to increased IL-27 and CD8+ T cell hyperactivation, exacerbating renal allograft rejection. siRNA knockdown of Zfp36 in p21high macrophages, mRNA stability assay for IL-27, macrophage-specific Zfp36 conditional KO mouse model, kidney transplantation model, IL-27 neutralizing antibody rescue Cell discovery Medium 40234384
2022 ZFP36 directly binds CDK6 mRNA ARE and reduces CDK6 expression; ZFP36-mediated CDK6 repression blocks cell cycle at G1 in prostate cancer cells, as confirmed by dual-luciferase and RIP assays. Dual-luciferase reporter assay, RIP, ZFP36 overexpression, cell cycle analysis, xenograft tumor model Oxidative medicine and cellular longevity Medium 36111167

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 RNA-binding protein ZFP36/TTP protects against ferroptosis by regulating autophagy signaling pathway in hepatic stellate cells. Autophagy 391 31679460
1991 Interleukin-6 signals activating junB and TIS11 gene transcription in a B-cell hybridoma. Molecular and cellular biology 164 1705005
1991 The TIS11 primary response gene is a member of a gene family that encodes proteins with a highly conserved sequence containing an unusual Cys-His repeat. Molecular and cellular biology 152 1996120
2014 A novel rice C2H2-type zinc finger protein, ZFP36, is a key player involved in abscisic acid-induced antioxidant defence and oxidative stress tolerance in rice. Journal of experimental botany 150 25071223
1989 Nucleotide sequence of a cDNA encoding TIS11, a message induced in Swiss 3T3 cells by the tumor promoter tetradecanoyl phorbol acetate. Oncogene 138 2915901
2014 Global target mRNA specification and regulation by the RNA-binding protein ZFP36. Genome biology 135 24401661
2014 ZFP36-FOSB fusion defines a subset of epithelioid hemangioma with atypical features. Genes, chromosomes & cancer 121 25043949
2018 ZFP36 RNA-binding proteins restrain T cell activation and anti-viral immunity. eLife 116 29848443
2021 Post-Transcriptional Regulation of Immune Responses and Inflammatory Diseases by RNA-Binding ZFP36 Family Proteins. Frontiers in immunology 115 34276705
2002 RNA binding properties of the AU-rich element-binding recombinant Nup475/TIS11/tristetraprolin protein. The Journal of biological chemistry 105 12324455
1996 Metal binding properties and secondary structure of the zinc-binding domain of Nup475. Proceedings of the National Academy of Sciences of the United States of America 87 8943007
2009 TIS11 family proteins and their roles in posttranscriptional gene regulation. Journal of biomedicine & biotechnology 82 19672455
2022 The ZFP36 family of RNA binding proteins regulates homeostatic and autoreactive T cell responses. Science immunology 76 36269839
2000 Similar but distinct effects of the tristetraprolin/TIS11 immediate-early proteins on cell survival. Oncogene 70 10763822
1995 Promoter analysis of Zfp-36, the mitogen-inducible gene encoding the zinc finger protein tristetraprolin. The Journal of biological chemistry 63 7559666
2013 mRNA-binding protein ZFP36 is expressed in atherosclerotic lesions and reduces inflammation in aortic endothelial cells. Arteriosclerosis, thrombosis, and vascular biology 57 23559629
2017 The ascorbate peroxidase APX1 is a direct target of a zinc finger transcription factor ZFP36 and a late embryogenesis abundant protein OsLEA5 interacts with ZFP36 to co-regulate OsAPX1 in seed germination in rice. Biochemical and biophysical research communications 55 29106954
2003 Selective RNA binding by a single CCCH zinc-binding domain from Nup475 (Tristetraprolin). Biochemistry 53 12705825
2012 Multiple functions of tristetraprolin/TIS11 RNA-binding proteins in the regulation of mRNA biogenesis and degradation. Cellular and molecular life sciences : CMLS 51 22968342
2007 ZFP36: a promising candidate gene for obesity-related metabolic complications identified by converging genomics. Obesity surgery 51 17546847
1991 A corrected sequence for the predicted protein from the mitogen-inducible TIS11 primary response gene. Oncogene 49 1861870
2006 Genetic variations in ZFP36 and their possible relationship to autoimmune diseases. Journal of autoimmunity 46 16546352
2016 Loss of ZFP36 expression in colorectal cancer correlates to wnt/ ß-catenin activity and enhances epithelial-to-mesenchymal transition through upregulation of ZEB1, SOX9 and MACC1. Oncotarget 45 27463018
1998 Characteristics of the intron involvement in the mitogen-induced expression of Zfp-36. The Journal of biological chemistry 43 9417109
2002 Identification of nuclear import and export signals within the structure of the zinc finger protein TIS11. Biochemical and biophysical research communications 41 12054509
2006 Functional characterization of iron-substituted tristetraprolin-2D (TTP-2D, NUP475-2D): RNA binding affinity and selectivity. Biochemistry 39 17087518
2021 ZFP36 Family Members Regulate the Proinflammatory Features of Psoriatic Dermal Fibroblasts. The Journal of investigative dermatology 38 34333017
1995 The yeast homologue YTIS11, of the mammalian TIS11 gene family is a non-essential, glucose repressible gene. Oncogene 36 7845673
2023 ZFP36-mediated mRNA decay regulates metabolism. Cell reports 35 37086408
2021 ZFP36 protects lungs from intestinal I/R-induced injury and fibrosis through the CREBBP/p53/p21/Bax pathway. Cell death & disease 35 34238924
2020 Circular RNA 000554 represses epithelial-mesenchymal transition in breast cancer by regulating microRNA-182/ZFP36 axis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 34 32729957
1994 The Drosophila TIS11 homologue encodes a developmentally controlled gene. Oncogene 34 7936658
1994 Cloning and characterization of ERF-1, a human member of the Tis11 family of early-response genes. DNA and cell biology 29 8024689
2014 Rapid proteasomal degradation of posttranscriptional regulators of the TIS11/tristetraprolin family is induced by an intrinsically unstructured region independently of ubiquitination. Molecular and cellular biology 28 25246635
1992 Sequence of a rat TIS11 cDNA, an immediate early gene induced by growth factors and phorbol esters. Gene 28 1511903
2015 Negative Feed-forward Control of Tumor Necrosis Factor (TNF) by Tristetraprolin (ZFP36) Is Limited by the Mitogen-activated Protein Kinase Phosphatase, Dual-specificity Phosphatase 1 (DUSP1): IMPLICATIONS FOR REGULATION BY GLUCOCORTICOIDS. The Journal of biological chemistry 27 26546680
2012 ZFP36 expression impairs glioblastoma cell lines viability and invasiveness by targeting multiple signal transduction pathways. Cell cycle (Georgetown, Tex.) 27 22544323
2016 Functional analysis of ZFP36 proteins in keratinocytes. European journal of cell biology 23 27182009
2022 Identification of ISG15 and ZFP36 as novel hypoxia- and immune-related gene signatures contributing to a new perspective for the treatment of prostate cancer by bioinformatics and experimental verification. Journal of translational medicine 22 35538543
2019 The mRNA-binding Protein TTP/ZFP36 in Hepatocarcinogenesis and Hepatocellular Carcinoma. Cancers 22 31717307
2018 Gambogic Acid Efficiently Kills Stem-Like Colorectal Cancer Cells by Upregulating ZFP36 Expression. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 22 29627822
2013 A masked PY-NLS in Drosophila TIS11 and its mammalian homolog tristetraprolin. PloS one 21 23951221
2024 Exosomal let-7a-5p derived from human umbilical cord mesenchymal stem cells alleviates coxsackievirus B3-induced cardiomyocyte ferroptosis via the SMAD2/ZFP36 signal axis. Journal of Zhejiang University. Science. B 20 38725341
2014 Association of BTG2, CYR61, ZFP36, and SCD gene polymorphisms with Graves' disease and ophthalmopathy. Thyroid : official journal of the American Thyroid Association 20 24780075
2010 Patterning a spiralian embryo: a segregated RNA for a Tis11 ortholog is required in the 3a and 3b cells of the Ilyanassa embryo. Developmental biology 20 20934422
2004 Recruitment of mRNA-destabilizing protein TIS11 to stress granules is mediated by its zinc finger domain. Experimental cell research 20 15652343
1998 Differential effects of sodium butyrate on the transcription of the human TIS11 family of early-response genes in colorectal cancer cells. British journal of biomedical science 20 10367403
2021 ZFP36 protects against oxygen-glucose deprivation/reoxygenation-induced mitochondrial fragmentation and neuronal apoptosis through inhibiting NOX4-DRP1 pathway. Brain research bulletin 19 34896479
2014 The Drosophila Tis11 protein and its effects on mRNA expression in flies. The Journal of biological chemistry 18 25342740
2020 ZFP36 Binds With PRC1 to Inhibit Tumor Growth and Increase 5-Fu Chemosensitivity of Hepatocellular Carcinoma. Frontiers in molecular biosciences 17 32766276
1994 A Drosophila melanogaster homolog of the TIS11 family of immediate early genes that can rescue a cdr1 cdc25 mutant strain of fission yeast. Gene 17 7828883
2018 Myeloid-specific deletion of Zfp36 protects against insulin resistance and fatty liver in diet-induced obese mice. American journal of physiology. Endocrinology and metabolism 16 29509432
2015 ZFP36 stabilizes RIP1 via degradation of XIAP and cIAP2 thereby promoting ripoptosome assembly. BMC cancer 16 25939870
2011 The mRNA-binding protein Zfp36 is upregulated by β-adrenergic stimulation and represses IL-6 production in 3T3-L1 adipocytes. Obesity (Silver Spring, Md.) 15 21818148
2000 Transcriptional activation function of zinc finger protein TIS11 and its negative regulation by phorbol ester. Biochemical and biophysical research communications 15 10913371
2023 ZFP36 loss-mediated BARX1 stabilization promotes malignant phenotypes by transactivating master oncogenes in NSCLC. Cell death & disease 14 37587140
1995 Increases in nup475 and c-jun are early molecular events that precede the adaptive hyperplastic response after small bowel resection. Annals of surgery 14 7618969
1995 Identification of a member of the TIS11 early response gene family at the insertion point of a DNA fragment containing a gene for the T-cell receptor beta chain in an acute T-cell leukemia. Oncogene 14 8545129
2020 MicroRNA-423 Drug Resistance and Proliferation of Breast Cancer Cells by Targeting ZFP36. OncoTargets and therapy 13 32158228
1998 Blastomeres and cells with mesendodermal fates of carp embryos express cth1, a member of the TIS11 family of primary response genes. The International journal of developmental biology 13 9551863
2025 Adipose ZFP36 protects against diet-induced obesity and insulin resistance. Metabolism: clinical and experimental 12 39761791
2025 ZFP36-family RNA-binding proteins in regulatory T cells reinforce immune homeostasis. Nature communications 12 40328742
2013 Comparative functional analysis of ZFP36 genes during Xenopus development. PloS one 12 23342169
2004 Expression of tristetraprolin (G0S24) mRNA, a regulator of tumor necrosis factor-alpha production, in synovial tissues of patients with rheumatoid arthritis. The Journal of rheumatology 12 15170914
2022 LncRNA MBNL1-AS1 Represses Proliferation and Cancer Stem-Like Properties of Breast Cancer through MBNL1-AS1/ZFP36/CENPA Axis. Journal of oncology 11 35518784
2017 Tis11 mediated mRNA decay promotes the reacquisition of Drosophila intestinal stem cell quiescence. Developmental biology 11 28445691
2024 Hydrogen peroxide positively regulates ABA signaling via oxidative modification of the C2H2-type zinc finger protein ZFP36 in rice. Plant physiology and biochemistry : PPB 10 38885566
2021 LINC00998 functions as a novel tumor suppressor in acute myeloid leukemia via regulating the ZFP36 ring finger protein/mammalian target of rapamycin complex 2 axis. Bioengineered 10 34699314
2021 Promoter Methylation Leads to Decreased ZFP36 Expression and Deregulated NLRP3 Inflammasome Activation in Psoriatic Fibroblasts. Frontiers in medicine 9 33585499
2021 ZFP36 promotes VDR mRNA degradation to facilitate cell death in oral and colonic epithelial cells. Cell communication and signaling : CCS 9 34380509
2021 MCM3AP-AS1 regulates proliferation, apoptosis, migration, and invasion of breast cancer cells via binding with ZFP36. Translational cancer research 9 35116304
1998 Expression and processing of G0/G1 switch gene 24 (G0S24/TIS11/TTP/NUP475) RNA in cultured human blood mononuclear cells. DNA and cell biology 9 9539105
2023 Endothelial Jagged1 levels and distribution are post-transcriptionally controlled by ZFP36 decay proteins. Cell reports 8 38157296
2022 Beta-hydroxybutyrate dampens adipose progenitors' profibrotic activation through canonical Tgfβ signaling and non-canonical ZFP36-dependent mechanisms. Molecular metabolism 8 35550189
2025 Targeting Zfp36 to combat cardiac hypertrophy: Insights into ferroptosis pathways. Clinical and translational medicine 7 40000392
2024 Persistent infection with Porphyromonas gingivalis increases the tumorigenic potential of human immortalised oral epithelial cells through ZFP36 inhibition. Cell proliferation 7 38351596
2024 ZFP36 Regulates Vascular Smooth Muscle Contraction and Maintains Blood Pressure. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 7 39589932
2022 Silencing lncRNA CDKN2B-AS1 Alleviates Childhood Asthma Progression Through Inhibiting ZFP36 Promoter Methylation and Promoting NR4A1 Expression. Inflammation 7 36422840
2015 Relationship between zinc finger protein 36 (ZFP36) gene polymorphisms and obstructive sleep apnea. Genetics and molecular research : GMR 7 26125882
2025 Senescence-induced p21high macrophages contributed to CD8+ T cells-related immune hyporesponsiveness in kidney transplantation via Zfp36/IL-27 axis. Cell discovery 6 40234384
2024 Regulation of Zfp36 by ISGF3 and MK2 restricts the expression of inflammatory cytokines during necroptosis stimulation. Cell death & disease 6 39117638
2023 The RNA-binding protein ZFP36 strengthens innate antiviral signaling by targeting RIG-I for K63-linked ubiquitination. Journal of cellular physiology 6 37565597
2022 Activation of the MKK3-p38-MK2-ZFP36 Axis by Coronavirus Infection Restricts the Upregulation of AU-Rich Element-Containing Transcripts in Proinflammatory Responses. Journal of virology 6 34985993
2022 ZFP36 Inhibits Tumor Progression of Human Prostate Cancer by Targeting CDK6 and Oxidative Stress. Oxidative medicine and cellular longevity 6 36111167
2020 Long noncoding RNA NNT-AS1 functions as an oncogene in breast cancer via repressing ZFP36 expression. Journal of biological regulators and homeostatic agents 6 32691576
2020 Wnt/CTNNB1 Signal Transduction Pathway Inhibits the Expression of ZFP36 in Squamous Cell Carcinoma, by Inducing Transcriptional Repressors SNAI1, SLUG and TWIST. International journal of molecular sciences 6 32784485
2012 Downregulation of the AU-rich RNA-binding protein ZFP36 in chronic HBV patients: implications for anti-inflammatory therapy. PloS one 6 22428029
2000 Cloning and characterization of the rat TIS11 gene. Molecular and cellular biochemistry 6 11129950
2024 Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines. BMC cancer 5 39026155
2024 LncRNA PCBP1-AS1 suppresses cell growth in oral squamous cell carcinoma by targeting miR-34c-5p/ZFP36 axis. Cellular and molecular biology (Noisy-le-Grand, France) 5 39380272
2023 ZFP36 ring finger protein like 1 significantly suppresses human coronavirus OC43 replication. PeerJ 5 36846448
2023 MiR-934 Exacerbates Malignancy of Gastric Cancer Cells by Targeting ZFP36. Iranian journal of public health 5 37744530
2022 A J-Protein OsDjC46 Interacts with ZFP36 to Participate in ABA-Mediated Antioxidant Defense in Rice. Antioxidants (Basel, Switzerland) 5 35204090
2022 FAM3D inhibits gluconeogenesis in high glucose environment via DUSP1/ZFP36/SIK1 axis. The Kaohsiung journal of medical sciences 5 36524461
2019 Tristetraprolin/ZFP36 Regulates the Turnover of Autoimmune-Associated HLA-DQ mRNAs. Cells 5 31817224
2024 Endotyping Eosinophilic Inflammation in COPD with ELAVL1, ZfP36 and HNRNPD mRNA Genes. Journal of clinical medicine 4 38337546
2025 Deletion of smooth muscle ZFP36 promotes neointimal hyperplasia in mice. Acta pharmacologica Sinica 3 39890944
2025 ZFP36 promotes ferroptosis and mitochondrial dysfunction and inhibits malignant progression in osteosarcoma by regulating the E2F1/ATF4 axis. Journal of pharmaceutical analysis 3 41050116
2024 Hydroxychloroquine attenuates double-stranded RNA-stimulated hyper-phosphorylation of tristetraprolin/ZFP36 and AU-rich mRNA stabilization. Immunology 3 39046234
2024 ZFP36, an RNA-binding protein promotes hBMSCs osteogenic differentiation via binding with JUN. Journal of orthopaedic surgery and research 3 39543732

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