Affinage

ZFP36L1

mRNA decay activator protein ZFP36L1 · UniProt Q07352

Length
338 aa
Mass
36.3 kDa
Annotated
2026-06-11
78 papers in source corpus 38 papers cited in narrative 41 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

ZFP36L1 is a CCCH tandem zinc-finger RNA-binding protein that recognizes AU-rich elements (AREs) in target mRNA 3'-UTRs and drives their post-transcriptional silencing, thereby controlling cell quiescence, lymphocyte development, angiogenesis, metabolism, and immune differentiation (PMID:15226444, PMID:27102483, PMID:31551365). It functions principally by destabilizing bound transcripts: it recruits the CCR4-NOT deadenylase complex to initiate decay, and in the case of viral and host RNAs engages both the XRN1 5'-3' and RNA-exosome 3'-5' degradation pathways (PMID:25106868, PMID:34643435). Beyond destabilization, ZFP36L1 represses translation directly through a CNOT1-dependent, deadenylation-independent mechanism that is distinct from the miRISC/4E-HP route used by its paralog TTP (PMID:32311426), and can interfere with 3'-end cleavage/polyadenylation of target pre-mRNAs (PMID:21832157). ARE recognition requires an intact tandem zinc-finger domain, mutation of which abolishes both RNA binding and downstream regulatory and antiproliferative activity (PMID:25014217, PMID:31551365, PMID:32556261). Its activity is gated by phosphorylation: RSK acting downstream of ERK phosphorylates the C-terminal region to dissociate CCR4-NOT and stabilize targets, while PKA phosphorylation at Ser-334 increases protein half-life and shifts partner engagement from CNOT1 toward the decapping coactivator Dcp1a (PMID:25106868, PMID:27708140); a C-terminal serine-rich cluster additionally governs cell cycle-dependent nuclear accumulation (PMID:32687160). Through ARE-mediated control of cell-cycle and signaling regulons, ZFP36L1 enforces quiescence and developmental checkpoints in B and T lymphocytes—including pre-BCR, beta-selection, and germinal-centre transitions—and shapes T-cell responses to TCR affinity and checkpoint blockade (PMID:27102483, PMID:27566829, PMID:28394372, PMID:38039407). Validated targets spanning these programs include VEGF/Dll4, Notch1, LDLR, BCL2, HIF1A/CCND1/E2F1, CDK6, Cyp7a1, Fgf21, and the neuroendocrine factors SOX2 and INSM1 (PMID:15467755, PMID:20622884, PMID:25106868, PMID:25014217, PMID:28891815, PMID:31551365, PMID:36008402).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2004 High

    Establishing that ZFP36L1 is a functional ARE-binding mRNA-destabilizing protein answered whether it acts directly on target transcripts and is biologically essential.

    Evidence ARE binding and stability assay on VEGF mRNA with RNP-IP and siRNA; knockout mouse plus cell-free deadenylation assays

    PMID:15226444 PMID:15467755

    Open questions at the time
    • Did not resolve the decay machinery recruited
    • Phosphorylation control not yet addressed
  2. 2006 Medium

    Polyribosome analysis in knockout embryos revealed that ZFP36L1 can act at the translational level, not only by altering mRNA stability.

    Evidence Polyribosome fractionation and mRNA stability measurement in conditional KO mouse embryos

    PMID:17013884

    Open questions at the time
    • Molecular basis of translational repression undefined
    • No interaction partner identified for this activity
  3. 2009 High

    Mapping ZFP36L1 to specific UAUUUAUU motifs in StAR mRNA defined the sequence determinants of target recognition and linked decay activity to steroidogenic output.

    Evidence RNA pull-down, ARE mutagenesis, reporter assay, and siRNA knockdown with cholesterol metabolism readout

    PMID:19179481

    Open questions at the time
    • Decay machinery recruited not characterized here
    • In vivo relevance not tested
  4. 2010 High

    Genetic work in lymphocytes showed ZFP36L1 (with ZFP36L2) suppresses developmental transcription factors, establishing its role in lymphopoiesis and tumor suppression.

    Evidence Conditional double-KO mice with RIP and genetic epistasis (Notch1 in thymopoiesis; Stat5b in erythroid progenitors)

    PMID:20622884 PMID:20702587

    Open questions at the time
    • Redundancy between paralogs not fully separated
    • Mechanism of decay vs translation control not dissected
  5. 2011 Medium

    Discovery that ZFP36L1 represses Dll4 by impairing 3'-end cleavage/polyadenylation extended its mechanistic repertoire beyond stability and translation.

    Evidence RIP, poly(A) signal mutagenesis, and mRNA cleavage/poly(A) ratio analysis

    PMID:21832157

    Open questions at the time
    • Generality of the 3'-end maturation mechanism across targets unknown
    • Factors mediating cleavage interference unidentified
  6. 2014 High

    Identification of CCR4-NOT recruitment and its release by RSK phosphorylation, plus PKA-driven partner switching, established how signaling kinases gate ZFP36L1 decay activity.

    Evidence Proteomic pull-down, in vitro kinase and co-IP assays with CCR4-NOT subunits, Cnot1 and Dcp1a; phosphosite analysis

    PMID:25106868 PMID:27708140

    Open questions at the time
    • Stoichiometry and dynamics of partner switching in vivo unresolved
    • Full set of regulatory kinases not defined
  7. 2014 High

    Demonstrating zinc-finger-dependent regulation of BCL2 and stress-responsive control of the mineralocorticoid receptor broadened the target landscape and tied ARE binding mechanistically to zinc-finger integrity.

    Evidence EMSA, 3'-UTR reporter, zinc-finger mutagenesis for BCL2; RIP, mutagenesis and in vivo water deprivation for MR

    PMID:24700863 PMID:25014217

    Open questions at the time
    • Decay machinery for these targets not mapped
    • Tissue-specific regulation incompletely defined
  8. 2016 High

    Genome-wide target identification in primary lymphocytes showed ZFP36L1 enforces quiescence by suppressing a cell-cycle regulon at developmental checkpoints.

    Evidence Conditional double-KO mice with genome-wide mRNA profiling and cell-cycle/quiescence assays in B cells and thymocytes

    PMID:27102483 PMID:27566829

    Open questions at the time
    • Direct vs indirect targets not fully separated transcriptome-wide
    • Contribution of each paralog not resolved
  9. 2017 High

    In vivo metabolic and B-cell identity studies extended ZFP36L1 function to bile-acid metabolism and marginal-zone B-cell positioning through defined ARE targets.

    Evidence Liver-specific and conditional KO mice; gain/loss of function with Cyp7a1 decay assay and KLF2/IRF8 transcriptome analysis

    PMID:28394372 PMID:28891815

    Open questions at the time
    • Upstream signals coupling FXR to ZFP36L1 activity incompletely mapped
    • Whether translation vs decay dominates per target not resolved
  10. 2018 Medium

    Domain mapping established the antiproliferative G1-arrest activity as zinc-finger-dependent and p53-independent, and linked C-terminal phosphorylation to cell-cycle behavior.

    Evidence TZF mutagenesis and cell-cycle analysis in isogenic p53 cell lines; cell synchronization with phosphorylation and spindle imaging

    PMID:29426877 PMID:29709483

    Open questions at the time
    • Spindle organization link rests on a single low-confidence method
    • Phosphorelay components not identified
  11. 2020 Medium

    Reconstitution showed ZFP36L1 represses translation via CNOT1 independent of deadenylation and through a mechanism distinct from miRISC, and mapped cell-cycle-dependent nuclear accumulation to a C-terminal serine cluster.

    Evidence In vitro mammalian translation system, IRES reporters, co-IP; cell fractionation with truncation and nuclear-targeting constructs

    PMID:32311426 PMID:32687160

    Open questions at the time
    • Molecular intermediary between ZFP36L1-CNOT1 and ribosome unknown
    • Trigger for nuclear elimination in S/G2 undefined
  12. 2020 Medium

    Antiviral studies demonstrated ZFP36L1 directly targets viral RNAs, repressing influenza transcripts translationally and destabilizing JEV genome RNA via dual XRN1/exosome decay.

    Evidence Zinc-finger mutagenesis, RIP, viral replication and RNA stability assays; XRN1/exosome knockdown epistasis

    PMID:32556261 PMID:34643435

    Open questions at the time
    • Determinants of decay-vs-translation choice on viral targets unclear
    • Breadth of antiviral spectrum not established
  13. 2019 High

    Cancer- and disease-model work expanded validated targets (HIF1A/CCND1/E2F1, HSP70) and tied ARE-mediated decay to hypoxia, proliferation, and osteoarthritis phenotypes.

    Evidence Systematic RNA pull-down with mutant controls, EMSA, transcriptome sequencing, and in vivo tumor/OA models

    PMID:30622281 PMID:31551365

    Open questions at the time
    • Context-dependence of target selection across tissues unresolved
    • Upstream regulators in these settings not fully mapped
  14. 2021 Medium

    Studies in plasma cells, T cells, and adipocyte/macrophage systems linked ZFP36L1 to homing, signaling adaptors, and metabolic differentiation through defined targets.

    Evidence Conditional KO with RNA-IP for GRK2/integrins; reporter and KO for Fgf21; co-IP showing 14-3-3/Caf1a-dependent Mkp-1 control; PPARγ2 reporter assays

    PMID:26180518 PMID:28206953 PMID:33306108 PMID:34774847

    Open questions at the time
    • Phospho-dependent stabilization mechanism (14-3-3) not generalized
    • Relative target hierarchy per cell type unclear
  15. 2022 High

    Epigenetic and EMT studies showed ZFP36L1 is itself transcriptionally controlled (LSD1 repression, SPI1/super-enhancer activation) and represses neuroendocrine and metastatic programs via SOX2/INSM1, ZEB2, and HDAC3.

    Evidence CRISPR screen, ChIP, RIP, mRNA stability and reporter assays in SCLC, gastric and liver cancer models

    PMID:36008402 PMID:36100056 PMID:39373630

    Open questions at the time
    • How upstream transcriptional inputs are integrated with phospho-regulation unknown
    • Causality of individual targets in tumor phenotypes incompletely separated
  16. 2023 Medium

    T-cell and metastasis studies positioned ZFP36L1 within signaling circuits, acting as a TCR-affinity sensor in an IL-2 feed-forward loop and suppressing TGF-β signaling via SDC4 decay.

    Evidence Conditional KO with in vivo competition assays; RIP, reporter and in vivo metastasis model for SDC4

    PMID:37935976 PMID:38039407

    Open questions at the time
    • Direct molecular targets of the affinity-sensing circuit not fully defined
    • Whether SDC4 effect is decay or translational not dissected
  17. 2024 Medium

    DNA-repair and proliferation studies linked ZFP36L1 to NHEJ (via DCLRE1C) and germinal-centre cell-cycle control with replication-stress consequences when lost.

    Evidence 3'-UTR binding and NHEJ/drug sensitivity assays; conditional double-KO with replication fork and DNA-damage-response analysis (preprint)

    PMID:41285712

    Open questions at the time
    • Germinal-centre findings remain a non-peer-reviewed preprint
    • Direct vs feedback contribution to CDK1/cyclin B1/p21 control not separated
  18. 2025 Medium

    Interactome and signaling studies in primary T cells defined the protein partners and upstream calcineurin/NFAT control of ZFP36L1 and its role in immunotherapy responses.

    Evidence BioID/MS interactome (UPF1, CNOT1, decay/P-body factors), pharmacological TCR-pathway dissection, and checkpoint-blockade tumor models (two preprints plus peer-reviewed promoter analysis)

    PMID:41211771

    Open questions at the time
    • Interactome and checkpoint findings are non-peer-reviewed preprints
    • Functional roles of UPF1 and stress-granule factors not mechanistically resolved
  19. 2026 Medium

    Recent disease-model work added CAMK2A and PRDM1 as targets linking ZFP36L1 to ferroptosis/mitochondrial dysfunction and Kupffer-cell inflammation.

    Evidence In vivo KO models with RIP and epistasis rescue (CAMK2A, PRDM1)

    PMID:41494598 PMID:42051151

    Open questions at the time
    • Single-lab target validations without independent replication
    • Decay vs translational mechanism per target not dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how ZFP36L1 selects between deadenylation, decapping, exosome/XRN1 decay, translational repression, and 3'-end interference on a given target, and how phospho-state and partner switching dictate that choice in vivo.
  • No structural model of ZFP36L1-machinery complexes
  • Rules governing decay-vs-translation outcome per transcript undefined
  • Quantitative map of phospho-states to interactomes in primary cells missing

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 8 GO:0045182 translation regulator activity 4 GO:0048018 receptor ligand activity 4 GO:0140098 catalytic activity, acting on RNA 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-1640170 Cell Cycle 4 R-HSA-168256 Immune System 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1266738 Developmental Biology 3
Partners
CNOT1DCP1ARSKUPF1XRN1YWHAB
Complex memberships
CCR4-NOT

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 ZFP36L1 (TIS11b) binds AU-rich elements in the 3'-UTR of VEGF mRNA and decreases its stability (half-life reduced from 130 to 60 min); RNP immunoprecipitation confirmed interaction in live cells; siRNA knockdown demonstrated TIS11b participates in basal and ACTH-induced VEGF mRNA expression control mRNA stability assay, RNP immunoprecipitation, siRNA knockdown, reporter assay Oncogene High 15467755
2004 Disruption of Zfp36l1 in mice causes embryonic lethality with chorioallantoic fusion defects and placental atrophy; Zfp36l1 has mRNA destabilization and deadenylation activities similar to TTP in cellular and cell-free assays Knockout mouse, cell-free RNA binding and deadenylation assays, cellular RNA destabilization assays Molecular and cellular biology High 15226444
2006 Zfp36l1 knockout embryos show elevated VEGF-A protein with enhanced association with polyribosomes (not altered mRNA stability), suggesting ZFP36L1 influences translational repression of VEGF-A in vivo Polyribosome fractionation, conditional knockout mouse, mRNA stability measurement Developmental dynamics Medium 17013884
2009 ZFP36L1/TIS11b binds UAUUUAUU repeats in the extended 3'-UTR of the 3.5-kb StAR mRNA and promotes its degradation; direct complex formation demonstrated; AURE mutations showed first two UAUUUAUU motifs required for TIS11b-mediated destabilization; siRNA knockdown of TIS11b enhanced 3.5-kb StAR mRNA levels and halved STAR protein induction with decreased cholesterol metabolism RNA pull-down, co-transfection reporter assay, site-directed mutagenesis of AREs, siRNA knockdown Molecular endocrinology High 19179481
2010 ZFP36L1 and ZFP36L2 bind evolutionarily conserved AU-rich elements in the 3'-UTR of Notch1 mRNA and suppress its expression; their combined deletion during thymopoiesis leads to elevated Notch1 and T-ALL development dependent on Notch1 Conditional double knockout mouse, RIP, reporter assay, genetic epistasis with Notch1 Nature immunology High 20622884
2010 ZFP36L1 binds the 3'-UTR of Stat5b mRNA via AU-rich elements and promotes its degradation, thereby negatively regulating erythroid differentiation of CD34+ hematopoietic progenitors mRNA binding assay, overexpression/knockdown, erythroid colony formation assay, luciferase reporter Molecular biology of the cell Medium 20702587
2011 TIS11b/ZFP36L1 binds to an AUUUA motif in the Dll4 mRNA 3'-UTR and represses Dll4 expression by interfering with mRNA 3'-end polyadenylation/cleavage efficiency, rather than mRNA stability — a novel mechanism for ZFP36L1 in mRNA 3'-end maturation RIP, reporter assay, poly(A) signal mutagenesis, mRNA cleavage/poly(A) ratio analysis Molecular biology of the cell Medium 21832157
2012 ZFP36L1 binds AU-rich elements in the BLIMP1 mRNA 3'-UTR and promotes its degradation, thereby negatively regulating plasmacytoid differentiation; shRNA knockdown of ZFP36L1 increased BLIMP1 mRNA and protein but not other differentiation factors (xbp1, irf4, bcl6); ZFP36L1 reduced activity of a BLIMP1 3'-UTR luciferase reporter shRNA knockdown, luciferase reporter assay, mRNA measurement, microarray network reconstruction PloS one Medium 23284928
2014 ZFP36L1 and ZFP36L2 bind the 3'-UTR of LDLR mRNA and recruit the CCR4-NOT deadenylase complex, causing mRNA destabilization; p90 ribosomal S6 kinase (RSK), downstream of ERK, directly phosphorylates the C-terminal regions of ZFP36L1/L2, causing dissociation of CCR4-NOT and stabilization of LDLR mRNA Proteomic RNA pull-down, kinase assay, co-IP with CCR4-NOT subunits, phosphorylation site analysis, antisense oligonucleotides Nucleic acids research High 25106868
2014 ZFP36L1 binds AU-rich elements in BCL2 mRNA 3'-UTR and promotes its degradation in B cells; zinc finger mutant ZFP36L1 failed to downregulate BCL2 3'-UTR reporter; removal of ARE core reduced ZFP36L1-mediated effect EMSA, luciferase 3'-UTR reporter assay, zinc finger mutagenesis, shRNA knockdown with mRNA stability measurement PloS one Medium 25014217
2014 Hypertonicity increases TIS11b/ZFP36L1 expression which binds a specific ARE motif in the mineralocorticoid receptor (MR) mRNA 3'-UTR, decreasing MR mRNA stability (~50% shorter half-life); RNA immunoprecipitation confirmed endogenous TIS11b physically interacts with MR mRNA; TIS11b knockdown prevented hypertonicity-induced MR repression in vivo Luciferase reporter with 3'-UTR mutants, site-directed mutagenesis, RNA immunoprecipitation, co-IP, knockdown, in vivo water deprivation model Journal of the American Society of Nephrology High 24700863
2015 ZFP36L1 binds AU-rich elements in the CDK6 mRNA 3'-UTR and negatively regulates CDK6 expression, thereby promoting monocyte/macrophage differentiation Lentiviral gain/loss of function, RIP/3'-UTR binding assay, differentiation assay Scientific reports Medium 26542173
2016 ZFP36L1 and ZFP36L2 suppress a posttranscriptional regulon of cell-cycle-promoting mRNAs to maintain quiescence in developing B lymphocytes before and after pre-BCR expression, thereby promoting VDJ recombination Conditional double knockout mouse, genome-wide mRNA analysis, cell cycle analysis, FACS-based quiescence assay Science High 27102483
2016 Zfp36l1 and Zfp36l2 regulate DNA damage response and cell cycle transcripts in thymocytes to enforce the beta-selection checkpoint; their targets were identified genome-wide in primary mouse thymocytes; absence of these RBPs allows DN3 thymocytes to acquire a post-selection gene expression profile despite lacking TCRβ Conditional double knockout mouse, genome-wide mRNA profiling of primary thymocytes, cell cycle analysis Journal of immunology High 27566829
2016 PKA activation phosphorylates TIS11b/ZFP36L1 at Ser-54 and Ser-334; phosphomimetic mutation at C-terminal S334 increased TIS11b half-life and enhanced mRNA decay activity; mimicking phosphorylation at S334 enhanced interaction with decapping coactivator Dcp1a, while preventing S334 phosphorylation potentiated interaction with CCR4-NOT subunit Cnot1 Site-directed mutagenesis, kinase assay, phosphosite immunodetection, co-IP with mRNA decay machinery components Molecular biology of the cell High 27708140
2017 ZFP36L1 is an FXR target gene; gain and loss of ZFP36L1 function reciprocally regulates Cyp7a1 mRNA levels and bile acid levels in vivo; ZFP36L1 promotes Cyp7a1 mRNA decay; mice lacking hepatic ZFP36L1 are protected from diet-induced obesity and steatosis through altered bile acid metabolism Conditional liver-specific knockout mouse, gain/loss of function, in vivo bile acid measurement, mRNA decay assay Journal of Clinical Investigation High 28891815
2017 ZFP36L1 controls the identity of marginal-zone B cells by limiting expression of transcription factors KLF2 and IRF8 post-transcriptionally via AU-rich element binding, and regulates a gene-expression program related to signaling, cell adhesion and locomotion; ZFP36L1 is specifically required for proper MZ B cell localization and survival Conditional knockout mouse, transcriptome analysis, flow cytometry, homing assay Nature immunology High 28394372
2018 ZFP36L1 inhibits cell proliferation and arrests the cell cycle at G1 in a cyclin D-dependent and p53-independent manner; TZF domain mutations abolish antiproliferative activity and cyclin D suppression; demonstrated in p53+/+ and p53-/- cells Overexpression, TZF domain mutagenesis, cell cycle analysis, knockdown in multiple cancer cell lines Scientific reports Medium 29426877
2018 ZFP36L1 phosphorylation is modulated in a cell cycle-dependent manner; the C-terminal region is critical for cell cycle-dependent phosphorylation; phosphorelay-dependent regulation of ZFP36L1 influences mitotic spindle organization Cell synchronization, subcellular fractionation, phosphorylation analysis, mitotic spindle imaging Biochemical and biophysical research communications Low 29709483
2019 ZFP36L1 binds the 3'-UTRs of HSP70 family members (HSPA1A) via AU-rich elements and promotes their mRNA decay; ZFP36L1 knockdown increases HSP70 expression and protects against OA; ZFP36L1 silencing abrogates experimental osteoarthritis in mice Adenovirus-mediated overexpression, genetic ablation, siRNA knockdown, in vivo OA model, mRNA stability assay Nature communications High 30622281
2019 ZFP36L1 binds AU-rich elements in the 3'-UTRs of HIF1A, CCND1, and E2F1 mRNAs and promotes their decay; wild-type but not zinc-finger mutant ZFP36L1 bound HIF1A 3'-UTR in EMSA and luciferase assays; ZFP36L1 suppresses hypoxia signaling and cell-cycle progression RNA pull-down with WT and mutant ZFP36L1, whole transcriptome sequencing, luciferase reporter, EMSA, in vitro and in vivo tumor models Cancer research High 31551365
2020 ZFP36L1 nuclear accumulation is cell cycle-dependent, prominent at G1/S boundary and reduced in S and G2 phases; the C-terminal serine-rich cluster is critical for regulating nuclear accumulation and cell cycle-dependent fluctuations; forced nuclear targeting led to ZFP36L1 elimination in S and G2 phases Cell fractionation, cell cycle synchronization, truncation mutant analysis, nuclear targeting constructs Journal of biochemistry Medium 32687160
2020 ZFP36L1 represses translation directly via AU-rich elements independent of deadenylation; interaction with CNOT1 is required for translational repression; unlike TTP, ZFP36L1 does not efficiently interact with 4E-HP or GIGYF2; ZFP36L1 translation repression is resistant to eIF4A inhibitor silvestrol, suggesting a distinct mechanism from miRISC In vitro mammalian translation system, IRES reporter assays, mutant protein functional assays, co-immunoprecipitation Biochimie Medium 32311426
2020 ZFP36L1 reduces influenza A virus (IAV) replication via translational repression of HA, M and NS viral RNA transcripts; ZFP36L1 directly binds IAV NS1 mRNA in the cytoplasm; CCCH zinc finger domain mutations abolished antiviral activity and NS1 mRNA binding Overexpression/knockdown, zinc finger domain mutagenesis, RIP, viral replication assay Nucleic acids research Medium 32556261
2021 ZFP36L1 destabilizes JEV genome RNA by targeting AU-rich element (AUUUA) motifs in the 3'-UTR and recruits both XRN1 (5'-3') and RNA-exosome (3'-5') decay pathways; zinc finger domain mutations disrupted RNA binding and antiviral activity Overexpression/knockdown, zinc finger mutagenesis, XRN1/exosome knockdown epistasis, viral RNA stability assay, 3'-UTR mapping Journal of virology Medium 34643435
2021 ZFP36L1 directly regulates G protein-coupled receptor kinase 2 (GRK2) and the integrin chains α4 and β1 mRNAs in splenic antibody-secreting cells (ASCs), limiting their abundance and facilitating ASC homing to the bone marrow; ZFP36L1-deficient ASCs accumulate in spleen and liver with diminished bone marrow accumulation Conditional knockout mouse, RNA-IP, flow cytometry, homing assay Journal of experimental medicine Medium 33306108
2021 ZFP36L1 directly binds AREs in the Fgf21 mRNA 3'-UTR and promotes its decay; wild-type but not zinc finger mutant ZFP36L1 decreased Fgf21 mRNA levels in luciferase reporter assays; liver-specific ZFP36L1 KO mice are protected from alcohol-induced hepatic steatosis, associated with elevated Fgf21 mRNA Liver-specific conditional knockout mouse, luciferase reporter, zinc finger mutant, RNA pull-down, in vivo alcohol model American journal of pathology High 34774847
2022 ZFP36L1 binds AU-rich elements in the ZEB2 mRNA 3'-UTR and promotes its degradation; ZFP36L1 silencing increases ZEB2 mRNA stability and promotes EMT in liver cancer cells; ZFP36L1 overexpression downregulates ZEB2 and abolishes EMT; ZEB2 3'-UTR is regulated by ZFP36L1 in luciferase reporter assays siRNA knockdown, overexpression, mRNA stability assay, luciferase 3'-UTR reporter, RNA-seq Cellular signalling Medium 36100056
2022 LSD1 binds and represses ZFP36L1; upon LSD1 inhibition, ZFP36L1 expression is restored and is sufficient to block SCLC neuroendocrine differentiation; ZFP36L1 binds and destabilizes SOX2 and INSM1 mRNAs (required for neuroendocrine differentiation); constitutive ZFP36L1 was required for LSD1 inhibitor sensitivity in a CRISPR screen Genome-wide CRISPR loss-of-function screen, overexpression, RIP, mRNA stability assay, ChIP for LSD1 Nature communications High 36008402
2023 ZFP36L1 promotes mRNA decay of SDC4 by binding AU-rich elements in its 3'-UTR, thereby inhibiting TGF-β signaling and suppressing osteosarcoma lung metastasis; SDC4 protects TGFBR3 from MMP-mediated cleavage, forming a positive SDC4-TGF-β feedback loop that ZFP36L1 inhibits Knockdown/overexpression, luciferase 3'-UTR reporter, RIP, in vivo metastasis model Oncogene Medium 37935976
2023 ZFP36L1 acts as a sensor of TCR affinity within an incoherent feed-forward loop, suppressing negative regulators of cytokine (IL-2) signaling to promote clonal expansion of high-affinity CD8 T cells; ZFP36L1 has a non-redundant role in establishing the dominance of high-affinity T cells through hierarchical IL-2 competition Conditional knockout mouse, adoptive transfer, in vivo competition assay, transcriptome analysis European journal of immunology Medium 38039407
2024 ZFP36L1, driven by a super-enhancer with SPI1 as the transcription factor, binds AU-rich elements in the HDAC3 mRNA 3'-UTR and promotes its decay, thereby reducing HDAC3-mediated transcriptional repression of PD-L1 and enhancing IFN-γ-induced PD-L1 expression in gastric cancer H3K27ac CUT&Tag, luciferase reporter, GST/RNA pull-down, ChIP/RIP, ChIP for SPI1, flow cytometry, in vivo functional assays eLife High 39373630
2024 ZFP36L1 directly binds AU-rich elements in the DCLRE1C mRNA 3'-UTR and promotes its degradation; ZFP36L1 overexpression reduces NHEJ DNA repair efficiency via DCLRE1C downregulation; decreased ZFP36L1 expression enables methotrexate resistance in osteosarcoma 3'-UTR binding analysis, overexpression/knockdown, NHEJ efficiency assay, drug sensitivity assay Cell death & disease Medium 41285712
2024 ZFP36L1 and ZFP36L2 restrain CDK1 and cyclin B1 expression in germinal centre B cells while controlling a p21-mediated negative feedback loop; absence of these RBPs causes G2-M arrest, DNA replication fork stalling, ATR/CHK1 activation, and apoptosis — resulting in curtailed germinal centre responses Conditional double knockout mouse, cell cycle analysis, DNA replication fork analysis, transcriptome profiling of GC B cells bioRxivpreprint Medium
2025 ZFP36L1 expression in CD8+ T cells is regulated by calcineurin/NFAT signaling (cyclosporin A potently inhibits ZFP36L1 but not ZFP36 expression); p38 MAPK, MEK1/2, and PKC contribute to inducing ZFP36L1; the Zfp36l1 promoter is enriched for NFAT binding sites while Zfp36 promoter has ELK-1/4 sites Pharmacological inhibitors of TCR signaling pathways, promoter analysis, in vitro T cell activation European journal of immunology Medium 41211771
2025 ZFP36L1 protein interacts with CNOT1 and components of mRNA decay, deadenylation, decapping, stress granule/P-body formation, and 5'-UTR-mediated translation repression in primary human T cells; the helicase UPF1 both interacts with ZFP36L1 protein and promotes its protein expression; the ZFP36L1 interactome is dynamic and partly RNA-dependent during T cell activation Proximity labeling (BioID), mass spectrometry, primary human T cells, RNA dependency analysis bioRxivpreprint Medium
2025 Anti-CTLA-4 or anti-LAG-3/PD-1 immunotherapy reduces ZFP36L1 expression in tumor-infiltrating CD4+ T cells, relieving post-transcriptional repression of Gzmb mRNA translation; constitutive ZFP36L1 abrogates the effects of anti-CTLA-4; deletion of ZFP36L1 (with ZFP36) triggers GzmB protein production and promotes tumor control In vivo tumor model with immune checkpoint blockade, conditional knockout, translational reporter assay, CRISPR bioRxivpreprint Medium
2026 ZFP36L1 promotes mRNA decay of CAMK2A by binding to its 3'-UTR AREs; ZFP36L1 knockout in CRS mice restores CAMK2A expression and attenuates ferroptosis and mitochondrial dysfunction; CAMK2A knockdown reverses the protective effects of ZFP36L1 depletion In vivo CRS mouse model with ZFP36L1 KO, RIP/binding assay, rescue experiments Clinical and translational medicine Medium 42051151
2026 ZFP36L1 promotes mRNA degradation of PRDM1 by binding AU-rich elements in its 3'-UTR in Kupffer cells, thereby suppressing inflammatory activation and ameliorating liver ischemia-reperfusion injury; PRDM1 overexpression reverses the suppressive effect of ZFP36L1 Rat DCD liver transplant model, LPS-stimulated Kupffer cells, overexpression vectors, RIP Biochimica et biophysica acta Medium 41494598
2015 In LPS-stimulated macrophages, ZFP36L1 is phosphorylated; hyper-phosphorylated ZFP36L1 stabilizes Mkp-1 mRNA by forming a complex with adapter protein 14-3-3 and decreasing interaction with deadenylase Caf1a; knockdown of ZFP36L1 increases basal Mkp-1 mRNA half-life siRNA knockdown, mRNA half-life assay, co-immunoprecipitation with 14-3-3 and Caf1a, LPS stimulation Journal of inflammation Medium 26180518
2017 ZFP36L1 binds the 3'-UTR of PPARγ2 (Pparγ2) mRNA and promotes its degradation, repressing adipogenic differentiation; ZFP36L1-containing RNP complexes contained less Pparγ2 mRNA; 3'-UTR reporter constructs demonstrated reduced luciferase in ZFP36L1-overexpressing cells Biotin pull-down, EMSA, luciferase reporter, RNP immunoprecipitation, transcriptional blockade kinetics Oncotarget Medium 28206953

Source papers

Stage 0 corpus · 78 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Deletion of the RNA-binding proteins ZFP36L1 and ZFP36L2 leads to perturbed thymic development and T lymphoblastic leukemia. Nature immunology 177 20622884
2004 Chorioallantoic fusion defects and embryonic lethality resulting from disruption of Zfp36L1, a gene encoding a CCCH tandem zinc finger protein of the Tristetraprolin family. Molecular and cellular biology 147 15226444
2016 RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence. Science (New York, N.Y.) 143 27102483
2004 Destabilization of vascular endothelial growth factor mRNA by the zinc-finger protein TIS11b. Oncogene 102 15467755
2006 The RNA binding protein Zfp36l1 is required for normal vascularisation and post-transcriptionally regulates VEGF expression. Developmental dynamics : an official publication of the American Association of Anatomists 83 17013884
2014 ZFP36L1 and ZFP36L2 control LDLR mRNA stability via the ERK-RSK pathway. Nucleic acids research 78 25106868
2000 Analysis of genes under the downstream control of the t(8;21) fusion protein AML1-MTG8: overexpression of the TIS11b (ERF-1, cMG1) gene induces myeloid cell proliferation in response to G-CSF. Blood 66 10887131
2019 RNA-binding protein ZFP36L1 regulates osteoarthritis by modulating members of the heat shock protein 70 family. Nature communications 65 30622281
2018 ZFP36L1 and ZFP36L2 inhibit cell proliferation in a cyclin D-dependent and p53-independent manner. Scientific reports 63 29426877
2016 The RNA-Binding Proteins Zfp36l1 and Zfp36l2 Enforce the Thymic β-Selection Checkpoint by Limiting DNA Damage Response Signaling and Cell Cycle Progression. Journal of immunology (Baltimore, Md. : 1950) 59 27566829
2017 Maintenance of the marginal-zone B cell compartment specifically requires the RNA-binding protein ZFP36L1. Nature immunology 53 28394372
2019 RNA-Binding Protein ZFP36L1 Suppresses Hypoxia and Cell-Cycle Signaling. Cancer research 52 31551365
2017 RNA-binding protein ZFP36L1 maintains posttranscriptional regulation of bile acid metabolism. The Journal of clinical investigation 51 28891815
2015 ZFP36L1 promotes monocyte/macrophage differentiation by repressing CDK6. Scientific reports 46 26542173
2009 cAMP-dependent posttranscriptional regulation of steroidogenic acute regulatory (STAR) protein by the zinc finger protein ZFP36L1/TIS11b. Molecular endocrinology (Baltimore, Md.) 38 19179481
2014 Post-transcriptional regulation of BCL2 mRNA by the RNA-binding protein ZFP36L1 in malignant B cells. PloS one 37 25014217
2022 Regulation of neuroendocrine plasticity by the RNA-binding protein ZFP36L1. Nature communications 36 36008402
1996 Distinct mechanisms for rescue from apoptosis in Ramos human B cells by signaling through CD40 and interleukin-4 receptor: role for inhibition of an early response gene, Berg36. European journal of immunology 35 8898945
2002 Identification of two novel ACTH-responsive genes encoding manganese-dependent superoxide dismutase (SOD2) and the zinc finger protein TIS11b [tetradecanoyl phorbol acetate (TPA)-inducible sequence 11b]. Molecular endocrinology (Baltimore, Md.) 32 12040026
2010 A novel concept in antiangiogenic and antitumoral therapy: multitarget destabilization of short-lived mRNAs by the zinc finger protein ZFP36L1. Oncogene 31 20802528
2010 ZFP36L1 negatively regulates erythroid differentiation of CD34+ hematopoietic stem cells by interfering with the Stat5b pathway. Molecular biology of the cell 30 20702587
2015 Functional regulation of Zfp36l1 and Zfp36l2 in response to lipopolysaccharide in mouse RAW264.7 macrophages. Journal of inflammation (London, England) 28 26180518
2020 The miR-93-3p/ZFP36L1/ZFX axis regulates keratinocyte proliferation and migration during skin wound healing. Molecular therapy. Nucleic acids 27 33473330
2018 The RNA-binding proteins Zfp36l1 and Zfp36l2 act redundantly in myogenesis. Skeletal muscle 25 30526691
2010 ZFP36L1 is regulated by growth factors and cytokines in keratinocytes and influences their VEGF production. Growth factors (Chur, Switzerland) 25 20166898
2009 Von Hippel-Lindau gene product modulates TIS11B expression in renal cell carcinoma: impact on vascular endothelial growth factor expression in hypoxia. The Journal of biological chemistry 24 19801654
2020 Zinc finger protein ZFP36L1 inhibits influenza A virus through translational repression by targeting HA, M and NS RNA transcripts. Nucleic acids research 22 32556261
2019 Epigenomic profiling of myelofibrosis reveals widespread DNA methylation changes in enhancer elements and ZFP36L1 as a potential tumor suppressor gene that is epigenetically regulated. Haematologica 22 30655376
2021 Efficient homing of antibody-secreting cells to the bone marrow requires RNA-binding protein ZFP36L1. The Journal of experimental medicine 20 33306108
2016 Regulation of StAR by the N-terminal Domain and Coinduction of SIK1 and TIS11b/Znf36l1 in Single Cells. Frontiers in endocrinology 19 27531991
1995 Insulin and insulin-like growth factor I stimulate expression of the primary response gene cMG1/TIS11b by a wortmannin-sensitive pathway in RIE-1 cells. FEBS letters 19 7615073
2018 ZFP36L1 and AUF1 Induction Contribute to the Suppression of Inflammatory Mediators Expression by Globular Adiponectin via Autophagy Induction in Macrophages. Biomolecules & therapeutics 16 30001609
2017 Zinc finger protein ZFP36L1 promotes osteoblastic differentiation but represses adipogenic differentiation of mouse multipotent cells. Oncotarget 16 28206953
2016 The cAMP pathway regulates mRNA decay through phosphorylation of the RNA-binding protein TIS11b/BRF1. Molecular biology of the cell 16 27708140
2023 Low expression of ZFP36L1 in osteosarcoma promotes lung metastasis by inhibiting the SDC4-TGF-β signaling feedback loop. Oncogene 15 37935976
2018 Levamisole suppresses adipogenesis of aplastic anaemia-derived bone marrow mesenchymal stem cells through ZFP36L1-PPARGC1B axis. Journal of cellular and molecular medicine 15 29993187
2011 A novel function of Tis11b/BRF1 as a regulator of Dll4 mRNA 3'-end processing. Molecular biology of the cell 15 21832157
2020 Overexpression of microRNA-129-5p in glioblastoma inhibits cell proliferation, migration, and colony-forming ability by targeting ZFP36L1. Bosnian journal of basic medical sciences 14 31999936
2024 Super-enhancer-driven ZFP36L1 promotes PD-L1 expression in infiltrative gastric cancer. eLife 13 39373630
2023 ZFP36L1 Promotes Gastric Cancer Progression via Regulating JNK and p38 MAPK Signaling Pathways. Recent patents on anti-cancer drug discovery 13 35611776
2019 Targeting AU-rich element-mediated mRNA decay with a truncated active form of the zinc-finger protein TIS11b/BRF1 impairs major hallmarks of mammary tumorigenesis. Oncogene 13 30914800
2024 MicroRNA-377-3p exacerbates chronic obstructive pulmonary disease through suppressing ZFP36L1 expression and inducing lung fibroblast senescence. Respiratory research 12 38317146
2021 ZFP36L1 Regulates Fgf21 mRNA Turnover and Modulates Alcoholic Hepatic Steatosis and Inflammation in Mice. The American journal of pathology 12 34774847
2007 Grape polyphenols affect mRNA expression of PGHS-2, TIS11b and FOXO3 in endometrium of heifers under ACTH-induced stress. Theriogenology 12 17825902
2023 The RNA binding proteins ZFP36L1 and ZFP36L2 are dysregulated in airway epithelium in human and a murine model of asthma. Frontiers in cell and developmental biology 11 37928904
2021 ZFP36L1 plays an ambiguous role in the regulation of cell expansion and negatively regulates CDKN1A in chronic myeloid leukemia cells. Experimental hematology 11 34090970
2014 Hypertonicity compromises renal mineralocorticoid receptor signaling through Tis11b-mediated post-transcriptional control. Journal of the American Society of Nephrology : JASN 11 24700863
2012 ZFP36L1 negatively regulates plasmacytoid differentiation of BCL1 cells by targeting BLIMP1 mRNA. PloS one 11 23284928
2008 Production and characterization of ZFP36L1 antiserum against recombinant protein from Escherichia coli. Biotechnology progress 11 18302406
2007 Strong induction of the Tis11B gene in myogenic differentiation. European journal of cell biology 10 17889962
2022 Silencing of RNA binding protein, ZFP36L1, promotes epithelial-mesenchymal transition in liver cancer cells by regulating transcription factor ZEB2. Cellular signalling 9 36100056
2021 Zinc Finger Protein ZFP36L1 Inhibits Flavivirus Infection by both 5'-3' XRN1 and 3'-5' RNA-Exosome RNA Decay Pathways. Journal of virology 9 34643435
2014 Myeloid ZFP36L1 does not regulate inflammation or host defense in mouse models of acute bacterial infection. PloS one 9 25299049
2023 Zfp36l1 establishes the high-affinity CD8 T-cell response by directly linking TCR affinity to cytokine sensing. European journal of immunology 8 38039407
2020 ARE-binding protein ZFP36L1 interacts with CNOT1 to directly repress translation via a deadenylation-independent mechanism. Biochimie 7 32311426
2024 ZFP36L1 controls KLF16 mRNA stability in vascular smooth muscle cells during restenosis after vascular injury. Journal of molecular and cellular cardiology 6 38653384
2021 Proteomic analysis of Laodelphax striatellus in response to Rice stripe virus infection reveal a potential role of ZFP36L1 in restriction of viral proliferation. Journal of proteomics 5 33711487
2020 Nuclear accumulation of ZFP36L1 is cell cycle-dependent and determined by a C-terminal serine-rich cluster. Journal of biochemistry 5 32687160
2020 Triciribine Engages ZFP36L1 and HuR to Stabilize LDLR mRNA. Molecules (Basel, Switzerland) 5 33019656
2024 Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma. Molecular cancer research : MCR 4 37801008
2021 The oncogenic role of HIF-1α/miR-182-5p/ZFP36L1 signaling pathway in nasopharyngeal carcinoma. Cancer cell international 4 34465330
1995 Identification of a functional promoter element in the 5'-flanking region of the rat cMG1/TIS11b gene. The Biochemical journal 4 7575462
2024 ZFP36L1 and ZFP36L2 reduce cyclin D1 expression by decreasing expression of E2F1 and long 3'UTR isoform of CCND1 transcripts. Molecular and cellular biochemistry 3 39110278
2022 Conflicting Roles of ZFP36L1 in Regulating the Progression of Muscle Invasive Bladder Cancer. Frontiers in molecular biosciences 2 35359594
2018 Novel phosphorelay-dependent control of ZFP36L1 protein during the cell cycle. Biochemical and biophysical research communications 2 29709483
2025 Combined Deletion of ZFP36L1 and ZFP36L2 Drives Superior Cytokine Production in T Cells at the Cost of Cell Fitness. European journal of immunology 1 40249077
2019 Author Correction: ZFP36L1 and ZFP36L2 inhibit cell proliferation in a cyclin D-dependent and p53-independent manner. Scientific reports 1 31745208
2026 ZFP36L1-mediated PRDM1 mRNA degradation inhibits inflammatory activation of Kupffer cells and ameliorates DCD liver ischemic-reperfusion injury. Biochimica et biophysica acta. Molecular basis of disease 0 41494598
2026 Bronchial epithelial-derived exosomal SLC6A14 promotes airway inflammation and mucus hypersecretion via the ZFP36L1/IL-8 axis. Functional & integrative genomics 0 41724861
2026 RNA-binding proteins Zfp36l1 and Zfp36l2 protect against premature thymic involution. Cellular & molecular immunology 0 41840035
2026 ZFP36L1 promotes non-small cell lung cancer progression under hypoxia by modulating CXCL9:SPP1 polarity: A single-cell transcriptomic study. Clinical and translational medicine 0 41906630
2026 Deficiency of ZFP36L1 and ZFP36L2 impairs liver homeostasis and initiates cholestatic liver injury. Hepatology communications 0 42008774
2026 RNA binding protein ZFP36L1 promotes ferroptosis in chronic rhinosinusitis by destabilizing CAMK2A mRNA and impairing mitochondrial quality control. Clinical and translational medicine 0 42051151
2026 ZFP36L1 Enhances Microglial Ferroptosis in Ischemic Stroke by Reducing FTO-Mediated N6-Methyladenosine Demethylation of ACSL1 mRNA. The Kaohsiung journal of medical sciences 0 42053094
2025 ZFP36L1 and L2 as novel antiviral factors for Crimean-Congo hemorrhagic fever virus via interaction with viral nucleoprotein. The Journal of biological chemistry 0 40749834
2025 Differential Regulation of TCR-Induced ZFP36 and ZFP36L1 Expression by Cyclosporin A in CD8+ T Cells. European journal of immunology 0 41211771
2025 Downregulation of ZFP36L1 contributes to methotrexate resistance in osteosarcoma through enhanced NHEJ DNA repair mechanisms. Cell death & disease 0 41285712
2022 [ZFP36L1 inhibits proliferation, invasion and migration of human breast cancer cells by inducing epithelial-mesenchymal transition through STAT3/p-STAT3 signaling pathway]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 35851086

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