Ask about this productRelated genes to: Taf6l Blocking Peptide
- Gene:
- TAF6L NIH gene
- Name:
- TATA-box binding protein associated factor 6 like
- Previous symbol:
- -
- Synonyms:
- PAF65A
- Chromosome:
- 11q12.3
- Locus Type:
- gene with protein product
- Date approved:
- 2001-12-03
- Date modifiied:
- 2015-11-20
Related products to: Taf6l Blocking Peptide
Related articles to: Taf6l Blocking Peptide
- 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 - Human SAGA is a 20-subunit transcriptional coactivator. Compared with yeast, metazoan SAGA uniquely incorporates a 150-kDa splicing-factor module (SPL), also present in U2 small nuclear ribonucleoprotein (U2snRNP). Metazoan gene duplication further specialized shared TFIID/SAGA subunits into SAGA-specific paralogs (TAF5L and TAF6L), but the functional consequences of this divergence are unknown. We report the structure of endogenous human SAGA purified via an affinity ligand from cells that were not disturbed by any genomic engineering tools. Our work reveals the high-resolution structure of SPL and the TAF6L HEAT repeat domain that provides the SPL with a docking surface. We elucidate how SPL and the HEAT repeats are incorporated into SAGA. We identify major structural differences between TAF6L/TAF5L and their canonical paralogs that enable SPL accommodation. SPL engages SAGA through a substantially smaller interface than in U2snRNP, despite sharing a deeply inserted helical motif. The seemingly weaker interaction of SPL with SAGA raises the possibility that SAGA relays this module to the splicing machinery. - Source: PubMed
Publication date: 2026/03/18
Damilot MylèneSchoeps ThomasTora LaszloSchultz PatrickLebeau LucPapai GaborBen-Shem Adam - Understanding how genes influence drug responses is critical for advancing personalized cancer treatments. However, identifying these gene-drug interactions in a physiologically relevant human system remains a challenge, as it requires a model that reflects the complexity and heterogeneity among individuals. Here we show that large-scale CRISPR-based genetic screens, including knockout, interference (CRISPRi), activation (CRISPRa), and single-cell approaches, can be applied in primary human 3D gastric organoids to systematically identify genes that affect sensitivity to cisplatin. Our screens uncover genes that modulate cisplatin response. By combining CRISPR perturbations with single-cell transcriptomics, we resolve how genetic alterations interact with cisplatin at the level of individual cells and uncover an unexpected link between fucosylation and cisplatin sensitivity. We identify TAF6L as a regulator of cell recovery from cisplatin-induced cytotoxicity. These results highlight the utility of human organoid models for dissecting gene-drug interactions and offer insights into therapeutic vulnerabilities in gastric cancer. - Source: PubMed
Publication date: 2025/08/14
Lo Yuan-HungHorn Hudson THuang Mo-FanYu Wei-ChiehYoung Chia-MeiLiu QingTomaske MadelineTowers MartinaDominguez AntoniaBassik Michael CLee Dung-FangQi Lei SWeissman Jonathan SChen JinKuo Calvin J - Although the tumor-stroma ratio (TSR) has prognostic value in many cancers, the traditional semi-quantitative visual assessment method has inter-observer variability, making it impossible for clinical practice. We aimed to develop a machine learning (ML) algorithm for accurately quantifying TSR in hematoxylin-and-eosin (H&E)-stained whole slide images (WSI) and further investigate its prognostic effect in patients with muscle-invasive bladder cancer (MIBC). We used an optimal cell classifier previously built based on QuPath open-source software and ML algorithm for quantitative calculation of TSR. We retrospectively analyzed data from two independent cohorts to verify the prognostic significance of ML-based TSR in MIBC patients. WSIs from 133 MIBC patients were used as the discovery set to identify the optimal association of TSR with patient survival outcomes. Furthermore, we performed validation in an independent external cohort consisting of 261 MIBC patients. We demonstrated a significant prognostic association of ML-based TSR with survival outcomes in MIBC patients ( < 0.001 for all comparisons), with higher TSR associated with better prognosis. Uni- and multivariate Cox regression analyses showed that TSR was independently associated with overall survival ( < 0.001 for all analyses) after adjusting for clinicopathological factors including age, gender, and pathologic stage. TSR was found to be a strong prognostic factor that was not redundant with the existing staging system in different subgroup analyses ( < 0.05 for all analyses). Finally, the expression of six genes (DACH1, DEEND2A, NOTCH4, DTWD1, TAF6L, and MARCHF5) were significantly associated with TSR, revealing possible potential biological relevance. In conclusion, we developed an ML algorithm based on WSIs of MIBC patients to accurately quantify TSR and demonstrated its prognostic validity for MIBC patients in two independent cohorts. This objective quantitative method allows application in clinical practice while reducing the workload of pathologists. Thus, it might be of significant aid in promoting precise pathology services in MIBC. - Source: PubMed
Publication date: 2023/02/01
Zheng QingyuanJiang ZhengyuNi XinmiaoYang SongJiao PanpanWu JiejunXiong LinYuan JingpingWang JingsongJian JunWang LeiYang RuiChen ZhiyuanLiu Xiuheng - Glioblastoma multiforme (GBM) is an aggressive form of brain tumours that remains incurable despite recent advances in clinical treatments. Previous studies have focused on sub-categorizing patient samples based on clustering various transcriptomic data. While functional genomics data are rapidly accumulating, there exist opportunities to leverage these data to decipher glioma-associated biomarkers. We sought to implement a systematic approach to integrating data from high throughput CRISPR-Cas9 screening studies with machine learning algorithms to infer a glioma functional network. We demonstrated the network significantly enriched various biological pathways and may play roles in glioma tumorigenesis. From densely connected glioma functional modules, we further predicted 12 potential Wnt/β-catenin signalling pathway targeted genes, including AARSD1, HOXB5, ITGA6, LRRC71, MED19, MED24, METTL11B, SMARCB1, SMARCE1, TAF6L, TENT5A and ZNF281. Cox regression modelling with these targets was significantly associated with glioma overall survival prognosis. Additionally, TRIB2 was identified as a glioma neoplastic cell marker in single-cell RNA-seq of GBM samples. This work establishes novel strategies for constructing functional networks to identify glioma biomarkers for the development of diagnosis and treatment in clinical practice. - Source: PubMed
Publication date: 2022/01/19
Xiang Chun-XiangLiu Xi-GuoZhou Da-QuanZhou YiWang XuChen Feng