ZFP36L2 antibody - center region (OAAB13102)
- Known as:
- ZFP36L2 (anti-) - central region (OAAB13102)
- Catalog number:
- oaab13102
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- ZFP36L2 antibody - center region (OAAB13102)
Related genes to: ZFP36L2 antibody - center region (OAAB13102)
- Gene:
- ZFP36L2 NIH gene
- Name:
- ZFP36 ring finger protein like 2
- Previous symbol:
- BRF2
- Synonyms:
- ERF2, RNF162C, TIS11D
- Chromosome:
- 2p21
- Locus Type:
- gene with protein product
- Date approved:
- 1995-05-09
- Date modifiied:
- 2016-10-05
Related products to: ZFP36L2 antibody - center region (OAAB13102)
Related articles to: ZFP36L2 antibody - center region (OAAB13102)
- Phenotypic plasticity is a hallmark of cancer; however the molecular switches required for cell-fate reprogramming are poorly understood. During intestinal wound-healing and colorectal cancer (CRC) metastasis, differentiated cells can dynamically dedifferentiate into an intestinal stem cell (ISC) state to drive epithelial regeneration and metastatic outgrowth. Here we show that the RNA-binding protein ZFP36L2, which is mutated in 5-10% of CRC, is a pivotal stress-responsive orchestrator of dynamic dedifferentiation. In mouse colon regeneration models, ZFP36L2 ablation inhibits dedifferentiation, ISC gene expression and function and impairs intestinal regeneration. In human CRC, loss of ZFP36L2 function abrogates metastatic seeding and the outgrowth of LGR5 canonical metastases while promoting lineage plasticity and non-canonical differentiation into heterogeneous cell states. Mechanistically, ZFP36L2 binds to stress-associated mRNAs that contain AU-rich 3' untranslated regions, which induces the formation of dynamic biomolecular condensates associated with mRNA degradation and termination of the stress response. Together, these data show that ZFP36L2 acts as an important molecular switch that couples stress sensing with phenotypic plasticity. This in turn drives cellular dedifferentiation essential for re-establishing the ISC state during wound healing and metastasis. In ZFP36L2-deficient CRC, the inability to re-enter the LGR5 state during metastatic outgrowth promotes non-canonical lineage plasticity, which is associated with poor clinical outcomes. - Source: PubMed
Publication date: 2026/08/05
Jiang QingwenRaghavan Manisha SRodriguez Aileen MLallo MorganTam Cyrus LHartner SaskiaForsyth BritneyMahmoud AhmedZincke FabianZhao HuiyongMoorman AndrewBalkaran SashaLuckett KathleenPintar JuraRomin YevgeniyChan EricSantella AnthonyMödl BernadetteShah FarheenBaali IlyesKharas Michael Gde Stanchina ElisaUrganci NilShia JinruPe'er DanaSanchez-Vega FranciscoKoche RichardMorris QuaidChan Joseph MGanesh Karuna - The ZFP36 family proteins (TTP, ZFP36L1, and ZFP36L2) are RNA-binding proteins that function as key post-transcriptional regulators of gene expression. They bind AU-rich elements (AREs) in target mRNA 3'UTRs, recruit the CCR4-NOT deadenylation complex to trigger mRNA decay, and maintain homeostasis in immunity, barrier function, and stem cell fate. Rather than acting on single targets, all family members share a conserved mRNA destabilization mechanism, with outcomes determined by member-specific expression, kinase-mediated regulation, and cell-type-dependent target availability. Dysregulation of this network stabilizes mRNAs encoding pro-inflammatory cytokines, immune checkpoints, and oncogenes, driving pathogenesis of inflammation, autoimmunity, cancer, cardiovascular and neurodegenerative diseases. Individual family members exert context-dependent and sometimes opposing effects, so their net function depends on the specific cellular and disease context. Therapeutic strategies targeting ZFP36 activity, including phosphatase agonism and epigenetic modulation, have shown promising preclinical results, but clinical translation remains early. This review summarizes the molecular regulatory networks of the ZFP36 family and their physiological and pathological roles, emphasizing the mechanistic principles that unify family-member function and the contextual factors that diversify it, to provide a foundation for future therapeutic development. - Source: PubMed
Publication date: 2026/07/17
Wen YuxuanPeng LichaoWang Jing - The zinc finger protein 36 (ZFP36) family, including ZFP36/tristetraprolin (TTP), ZFP36 CCCH-type-like 1 (ZFP36L1), and ZFP36 CCCH-type-like 2 (ZFP36L2), consists of conserved CCCH-type tandem zinc-finger RNA-binding proteins. These proteins recognize AU-rich elements (AREs) in target mRNAs and promote deadenylation, decay, and translational repression. In this review, we use the term post-transcriptional immune checkpoint in a restricted conceptual sense: ZFP36 family proteins are intracellular, RNA-level negative regulators that tune the magnitude, duration, and resolution of immune effector programs, rather than classical receptor-ligand immune checkpoints such as programmed cell death protein 1 (PD-1)/ programmed death-ligand 1 (PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). We summarize structural features, ARE-recognition mechanisms, mRNA decay pathways, translational repression mechanisms, and post-translational regulation of the ZFP36 family, while explicitly distinguishing mechanisms established for ZFP36 from those inferred for ZFP36L1 and ZFP36L2. We then review cell-type-specific roles in innate and adaptive immunity, including myeloid inflammatory responses, barrier tissue inflammation, innate lymphoid cell function, T cell activation and effector differentiation, regulatory T cell stability, B cell development, and antiviral immunity. In cancer, ZFP36 family members show context-dependent functions that should be separated into tumor-cell-intrinsic effects and immune-microenvironment-dependent effects. They suppress tumor progression by destabilizing pro-inflammatory, angiogenic, metabolic, and epithelial-mesenchymal transition (EMT)-associated transcripts, yet may also restrict antitumor immune responses or promote immune evasion in selected tumor contexts. Finally, we discuss autoimmune and inflammatory diseases, allergic disorders, transplant immunity, neuroimmune relevance, and therapeutic strategies, emphasizing the current evidentiary limits, preclinical status, and safety concerns of ZFP36 family modulation. - Source: PubMed
Publication date: 2026/07/13
Yang YutingZhong WenhaoHuang QiangLiu ZichangWu YanweiLuo LingjieChen Liang - Urinary tract infections (UTIs) are among the most common bacterial infections, yet the genetic factors influencing susceptibility remain poorly understood. We performed a genome-wide association study of recurrent UTI involving 1,860,836 individuals (213,869 cases and 1,646,967 controls). We identified 36 independent non-HLA genome-wide significant loci encoding kidney epithelial and immune response genes and demonstrated that some loci have sex-specific effects. Integrative functional annotation, expression and protein quantitative trait locus colocalization, and single-cell multi-omic analyses revealed that UTI risk alleles preferentially modulated gene expression in kidney, ureter, and bladder epithelia. Multi-omic prioritization converged on a number of pathogenic pathways: epithelial barrier and mucosal glycocalyx defense (, , , ), innate immune regulation (, , ), infection resolution and regulated cell death (, , ), epithelial identity maintenance (, , ), urinary tract development (, , , , ), and nutritional immunity through iron sequestration (). Approximately one-third of loci colocalized with gene expression in kidney tubules, suggesting direct modulation of epithelial host-defense programs. Among all loci, , which encodes a GPI-anchored epithelial surface protein expressed in the kidney papilla and urinary tract epithelia, emerged as the strongest candidate causal gene. We demonstrated that PSCA was secreted into urine, bound uropathogenic , and inhibited bacterial growth , implicating it as a constitutive epithelial defense factor. We also demonstrated that while was protective against urinary infections and duodenal ulcers, it was associated with increased risk of bladder, prostate, and gastric cancers, suggesting antagonistic pleiotropy between mucosal defenses and oncogenesis. Together, our findings define the polygenic architecture of UTI susceptibility, highlighting epithelial surface defense, innate immune regulation, developmental patterning, and nutritional immunity as central components of host defense, providing a new framework for host-directed, non-antibiotic interventions. - Source: PubMed
Publication date: 2026/07/10
Xu KatherineKhan AtlasShang NingZeng WenjieWang ChenBerrouet CeciliaShen Tian HuaiNarayanan PadmaDeng JennyDiPerna ChiaraWilliams CharlotteCuacuas SarahOlsen Timothy RArace JeffreyGhotra AryanMonical WayneBorisov OlegHaug StefanLiu HongboHa EunjiBanlengchit RunLevitman AbrahamPatel DiyaChou ClaireHalibart BartlomiejGuo Tai WeiSimmons ShawnGoswami SanyaNesanir KivancFujita MasashiKullo Iftikhar JJarvik Gail PWei Wei-QiFeng QiPingJiang LanStein C MichaelWeng ChunhuaHripscak GeorgeGharavi Ali GSusztak KatalinDe Jager Philip LKöttgen AnnaBarasch JonathanSims Peter AKiryluk Krzysztof - The thymus generates immunocompetent T cells, but its function declines with age. Thymic activity relies on proper differentiation of thymic epithelial cells (TECs), which establish unique niches for T-cell development. However, the molecular mechanisms governing the differentiation of functional cortical (c) and medullary (m) TEC subsets from common progenitors remain poorly understood. Using dual conditional knockout (dcKO) and lineage-tracing mouse models, we demonstrated that RNA-binding proteins ZFP36L1 and ZFP36L2 cooperatively maintain a functional TEC microenvironment. TEC-specific deletion of Zfp36l1 and Zfp36l2 in dcKO mouse models led to early-onset thymic hypoplasia and a marked reduction in TEC and thymocyte numbers. Mechanistically, single-cell transcriptomics revealed significant alterations in the composition and transcriptional programs of cTECs, mTECs, and thymic mimetic cells, linking Zfp36l1 and Zfp36l2 deficiency to a widespread increase in metabolic gene dysregulation in adult dcKO TECs. The erosion of the TEC compartment and the accumulation of age-associated TECs suggested impaired differentiation of mature lineages from their progenitors. Concordantly, fate-mapping analysis revealed that dual deficiency in Zfp36l1 and Zfp36l2 disrupted the canonical developmental trajectory from β5t-expressing TEC progenitors into mature TECs. Our findings uncover a previously unappreciated layer of post-transcriptional regulation in TEC biology, identifying a cooperative role for ZFP36L1 and ZFP36L2 in orchestrating TEC differentiation to sustain thymic function and prevent premature involution. - Source: PubMed
Publication date: 2026/06/24
Ferreirinha PedroRodrigues Pedro MSobral FranciscoCavadas BrunoPinheiro Rúben G RRocha Ana MafaldaTakahama YousukeTurner MartinAlves Nuno L