Ask about this productRelated genes to: IKZF2 antibody
- Gene:
- IKZF2 NIH gene
- Name:
- IKAROS family zinc finger 2
- Previous symbol:
- ZNFN1A2
- Synonyms:
- Helios
- Chromosome:
- 2q34
- Locus Type:
- gene with protein product
- Date approved:
- 1999-08-23
- Date modifiied:
- 2016-10-05
Related products to: IKZF2 antibody
Related articles to: IKZF2 antibody
- IKAROS, HELIOS, and AIOLOS are transcription factors predominantly expressed in hematopoietic cells, where they form heteromeric and homodimeric complexes and facilitate transcriptional regulation. IKZF proteins also associate with non-IKZF family proteins, which vary between different immune cell subtypes and their differentiation stages. Heterozygous germline loss-of-function variants in , , and cause IKAROS, HELIOS, and AIOLOS deficiencies, respectively, leading to inborn errors of immunity (IEI). Heterozygous gain-of-function (GOF) variants in result in IKAROS-GOF disease, characterized by autoimmune and allergic manifestations, whereas dominant-negative IKAROS and AIOLOS variants are associated with combined immunodeficiency. Importantly, patients with IKZF-associated IEI exhibit varying degrees of immunodeficiency, immune dysregulation, and occasional malignancies, and so, disease manifestations differ significantly among the variant types. Therefore, each variant often causes phenotypic heterogeneity, which possibly stems from diverse protein complexes formed by IKZF proteins. Besides immunoglobulin supplementation for patients with B cell defects and hematopoietic cell transplantation for severe cases, molecularly targeted therapies have been investigated for treating IKAROS-GOF disease. - Source: PubMed
Publication date: 2025/07/18
Yamashita MotoiMorio Tomohiro - Recent studies have advanced understanding of chromosomal organization and its role in gene regulation, yet most analyses focus on short-range interactions (<2 Mb), limiting insight into broader architecture. The relationships between topologically associating domains (TADs), sub-TAD loops, cross-TAD interactions, and chromosomal compartmentalization remain poorly understood. Here, using high-resolution Hi-C analysis, we identify extensive multi-megabase and interchromosomal interactions (metaloops) in T lymphocytes that organize into meta-TAD associations (metadomains). These metaloops connect distal promoters and regulatory elements of genes functionally important in T cells, including Ctla4, Ikzf2, Il2ra, Ets1, and Foxo1. Reanalysis of mouse and human datasets confirms their reproducibility and dependence on superenhancers. Genome-wide clustering reveals three distinct interchromosomal hubs, including a superenhancer-enriched hub linked to T cell-specific gene activation. Integrative analysis of regulatory genomics data identifies factors associated with short- versus long-range interactions. This study introduces a broadly applicable computational framework and reveals features of T cell genome organization. - Source: PubMed
Publication date: 2026/05/07
Dolsten GabrielWang Zhong-MinHuang XiaoSong SusieWilson Michael JBing Xin YangKe WenfanCafiero Thomas RNelson Amy NFernando SebastianPloss AlexanderSchedl PaulLevine Michael SViny Aaron DRudensky Alexander YPritykin Yuri - Targeted protein degradation (TPD) is a therapeutic strategy that utilizes small molecules to induce the proximity-driven degradation of disease-causing proteins. Because the efficacy and selectivity of TPD compounds must be validated across thousands of proteins, high-throughput proteomics is essential for the rapid screening and characterization of these novel degraders. Here, we developed a 300 samples per day (SPD) LC-MS/MS method using the Orbitrap Astral mass spectrometer for ultrahigh-throughput TPD compound screening. We identified close to 8000 protein groups from a single cell line with a coefficient of variation (CV) of less than 10%, highlighting the deep proteome coverage and method reproducibility even at 300 SPD. This high degree of precision provides the statistical confidence to detect subtle, yet significant, changes in protein abundance that were previously challenging to quantify in high-throughput workflows. To evaluate the quantitation accuracy of this method, we further mixed the digests from two or three species at different ratios. Our three-proteome mixture results demonstrated highly accurate quantitation for proteins with both small and large fold changes. Moreover, our two-proteome mixture experiment, where 20 to 160 ng of yeast digest was spiked into 200 ng of HeLa digest, showed an R of 0.999 for the yeast proteome, underscoring the quantitation accuracy of the method. Utilizing this workflow, we studied dose-dependent protein degradation patterns induced by pomalidomide, iberdomide, and mezigdomide. Our results indicate that mezigdomide may possess enhanced efficacy in T cells by degrading additional proteins such as IKZF2, thereby boosting anticancer immunity. Together, we developed an ultrahigh-throughput LC-MS/MS method with excellent proteome coverage and quantitation accuracy that is highly suitable for chemoproteomics screening of drug libraries. - Source: PubMed
Publication date: 2026/05/05
Lin HanfengYang Yen-YuMaity SudipaSun QingyuWang Jin - Immunosuppressive Tregs, regulated by IKZF2, facilitate tumor immune evasion and resistance to immune checkpoint therapies. Targeted IKZF2 degradation represents a promising strategy for the development of innovative cancer immunotherapeutics. Herein, we designed and synthesized a novel series of phthalazinone-based glutarimide derivatives, identifying compound as a potent, highly selective, and rapid-acting IKZF2 molecular glue degrader. Compound induced robust IKZF2 degradation (DC = 1.78 nM and = 93.2%) via a Cullin-CRBN-dependent pathway, while sparing other CRBN neosubstrates and outperforming the benchmark degrader DKY709. Mechanistically, -induced IKZF2 deletion enhanced the proinflammatory IL-2 production and attenuated the immunosuppressive function of Tregs. Oral administration of triggered rapid, profound, and sustained IKZF2 degradation in mice spleen and thymus. As monotherapy, significantly suppressed B16F tumor growth, and combined with anti-PD-1 antibody therapy exhibited marked synergistic effects. Together, our findings demonstrate as a promising IKZF2 degrader for advancing cancer immunotherapy. - Source: PubMed
Publication date: 2026/04/07
Wang YaleiQi ZhenzeSun ShiyangWei TingWei PengliJia ChangkaiCai XuZhao ZhiyuanQiao MinZou YaxinMu ZhihuiLei XiaofangZhang ZiyunWei XinnaQi JiataoCui SihanYang TingtingZhuang XiaomeiXiao JunhaiZheng ZhibingShang HongzhouLi PengyunLi Song - Regeneration and expansion of Treg by low-dose interleukin-2 (IL-2) therapy is considered a potential treatment strategy for a wide range of autoimmune diseases. To provide a pathophysiologically-based rationale for low-dose IL-2 therapy, we investigated whether reversible defects in the Treg-IL-2 axis emerge in inflammatory myopathies. - Source: PubMed
Publication date: 2026/03/25
Ohmes JustusMonne Luisa RComdühr SaraGerlach FynnGrasshoff HannaDübbers AlexanderMüller AntjeScheffold AlexanderRiemekasten GabrielaAkbarzadeh RezaHumrich Jens Y