Ask about this productRelated genes to: GCN5L2 antibody
- Gene:
- KAT2A NIH gene
- Name:
- lysine acetyltransferase 2A
- Previous symbol:
- GCN5L2
- Synonyms:
- GCN5, PCAF-b
- Chromosome:
- 17q21.2
- Locus Type:
- gene with protein product
- Date approved:
- 1996-12-17
- Date modifiied:
- 2016-10-05
Related products to: GCN5L2 antibody
Related articles to: GCN5L2 antibody
- The transcription factor p63 is critical for epithelial development and implicated in tumorigenesis. However, our understanding of the role of p63 in development and disease has been complicated by its diverse isoforms. As a member of the p53 family member of genes, encodes for numerous isoforms, including the N-terminal variants TAp63 and ΔNp63, which are generated through alternative promoter usage. TAp63 and ΔNp63 share various structural domains, including the DNA-binding domain, and primarily differ in their N-terminus which consists of intrinsically disordered regions (IDRs). The isoforms are known to have different functions, including tumor suppression in the case of TAp63 and pro-tumor formation for ΔNp63, but how the N-terminus contributes to isoform-specific gene regulatory effects has yet to be elucidated. Using both genomic and TurboID proximity-labeling proteomic approaches, we show that the N-terminus mediates differential interactions with cofactors that have direct effects on isoform function, specifically the regulation of apoptosis. We find that the N-terminus of TAp63 interacts with more transcriptional machinery, leading to stronger transcriptional activity by TAp63 than ΔNp63. However, ΔNp63 maintains interactions with coactivators, suggesting it can retain some transactivation capabilities. Strikingly, the N-terminus of TAp63 displays enriched interactions with chromatin modifiers, including the histone acetyltransferase KAT2A, that result in TAp63-specific binding at inaccessible sites. We find that an IDR-mediated interaction with KAT2A is involved in regulation of apoptosis by TAp63. Collectively, our results suggest a model in which TAp63 and ΔNp63 broadly share genomic occupancy, but differential interactions with cofactors contribute to isoform-specific regulation by TAp63 and ΔNp63. - Source: PubMed
Publication date: 2026/04/22
Nogueira Marina FMoore Michael JBiswas Aparna RMeers Michael PPuram Sidharth V - Psoriasis frequently relapses after treatment withdrawal, consistent with persistent epigenetic programs in lesional immune cells. Lysine acetylation is a reversible regulatory layer linking chromatin accessibility, transcription factor activity, and immune-cell effector programs; yet, its cell-type-resolved landscape and clinical stratification value in psoriasis remain incompletely defined. We integrated four bulk transcriptome cohorts of psoriatic and healthy skin (746 psoriasis, 515 controls) with two public skin scRNA-seq datasets. A diagnostic acetylation-regulator signature was derived from 33 curated acetylation regulators, and acetylation endotypes were defined by unsupervised clustering. The cell-type-specific expression was mapped at the single-cell resolution. Key regulators were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in an imiquimod-induced psoriasis-like mouse model, and further verified in an independent dataset (GSE136757). Motif enrichment and drug-target mining were used to prioritize transcriptional regulators and candidate epigenetic therapeutics. Sixteen acetylation regulators were differentially expressed in bulk skin, with histone deacetylase (HDAC1) showing the strongest upregulation and lysine acetyltransferase (KAT2A) the strongest downregulation. A 13-gene acetylation signature discriminated psoriasis from controls (area under the curve, AUC 0.886) and separated lesional samples into two acetylation endotypes with divergent pathway states (hypoxia-glycolysis versus oxidative-stress-dominated programs). Single-cell mapping demonstrated immune-restricted acetylation modules, including CREB binding protein (CREBBP)-enriched neutrophils, histone deacetylase 1 (HDAC1)-high cluster of differentiation (CD)8 T cells, and lysine acetyltransferase 6A (KAT6A)/lymphoid enhancer binding factor (LEF1)-enriched CD4 and regulatory T cell (Treg) subsets, coincident with interleukin (IL)-17-related inflammatory programs. In mice, qRT-PCR confirmed the coordinated dysregulation of hub genes and highlighted Hnf1a and Kat6a as reproducible candidates. External validation using the GSE136757 dataset further supports their robust diagnostic performance. Motif analysis nominated interferon regulatory factor (IRF4), YY transcription factor (YY2), and zinc finger protein (ZNF404) as putative transcriptional mediators downstream of acetylation programs, and drug-target mining prioritized epigenetic compounds with subtype-relevant potential, including histone deacetylase (HDAC) inhibitors (e.g., entinostat) and the p300/CREB binding protein (CBP) inhibitor A485. This integrative atlas links acetylation regulators to specific immune compartments, defines acetylation endotypes associated with distinct inflammatory programs, and provides a rationale for stratified epigenetic target selection in psoriasis. - Source: PubMed
Publication date: 2026/04/01
Xie MengjiMa XiaoxuanZhang YingKuai LeLuo YingSong JiankunDing XiaojieRu YiLuo YueFei XiaoyaHong SeokgyeongDeng GuoshuSu YonghuaWang RuipingLi BinXiang YanweiLi MiaoZhou Mi - NFS1 (cysteine desulfurase), an essential enzyme in iron-sulfur (FeS) cluster biogenesis, is a key regulator of ferroptosis. In oral squamous cell carcinoma (OSCC), NFS1 is up-regulated and undergoes enhanced succinylation under glucose starvation. This study aims to elucidate the mechanistic role of NFS1, particularly through ferroptosis, in OSCC progression. - Source: PubMed
Publication date: 2026/04/23
Ling HangQing LiminZuo LiangWang HonghanCai XuLiu YanTian Hao - Traumatic brain injury (TBI) remains a leading global cause of morbidity and mortality. Xingnaojing injection (XNJI) and acupuncture, two traditional Chinese medicine (TCM) modalities, are widely utilized in treating various neurological disorders, including TBI. - Source: PubMed
Publication date: 2026/04/24
Yu LimeiWang YakunWu WeihuaAn PengYu Zhenfei - The Spt-Ada-Gcn5 acetyltransferase (SAGA) complex regulates gene expression through histone acetylation at promoters, mediated by its histone acetyl transferase (HAT), KAT2A. While SAGA structure and function are well characterised, mechanisms controlling the stability of individual subunits, including KAT2A, remain unclear. Here, using a fluorescence-based KAT2A stability reporter, we systematically dissect the molecular dependencies controlling KAT2A protein abundance, and identify the non-enzymatic SAGA CORE module subunits-TADA1, TAF5L, and TAF6L- as necessary for KAT2A stability. Loss of these subunits disrupts SAGA complex integrity, leading to non-chromatin-bound KAT2A that is degraded by the proteasome and consequent reduced H3K9 acetylation. Proteomic profiling reveals progressive loss of components from the CORE and HAT modules upon acute SAGA CORE disruption, indicating that an intact CORE is required for the stability of numerous SAGA components. Finally, a focused CRISPR screen of ubiquitin-proteasome system genes identifies the E3 ligase UBR5, a known regulator of orphan protein degradation, and the deubiquitinase OTUD5, as regulators of KAT2A degradation when the SAGA CORE is perturbed. Together, these findings reveal a dependency of KAT2A protein stability on SAGA CORE integrity and define an orphan quality control mechanism targeting unassembled KAT2A, revealing a potential vulnerability in SAGA-driven malignancies. - Source: PubMed
Publication date: 2026/04/20
Batty PaulBeneder HannahSchätz CarolineOnea GabrielZaczek MaciejKutschat Ana PAbele MiriamMüller SophieSuperti-Furga GiulioWinter Georg ESeruggia Davide