Ask about this productRelated genes to: SH3BGRL Blocking Peptide
- Gene:
- SH3BGRL NIH gene
- Name:
- SH3 domain binding glutamate rich protein like
- Previous symbol:
- -
- Synonyms:
- MGC117402
- Chromosome:
- Xq21.1
- Locus Type:
- gene with protein product
- Date approved:
- 1998-01-21
- Date modifiied:
- 2016-10-05
Related products to: SH3BGRL Blocking Peptide
Related articles to: SH3BGRL Blocking Peptide
- Gastric cancer remains highly lethal, yet how protein S-palmitoylation shapes tumour ecosystems and clinical outcome is unclear. We integrated single-cell RNA sequencing (119,931 cells from 25 gastric tumours) with spatial transcriptomics and bulk cohorts to delineate palmitoylation-linked states across malignant, immune, and stromal compartments. A palmitoylation-high malignant programme partitioned into three metastasis-enriched subclusters with increased fatty-acid metabolism and Ras-MAPK signalling and predicted worse survival. Spatial mapping and ligand-receptor inference revealed co-localised niches where palmitoylation-high tumour cells interacted with immunosuppressive myeloid cells and distinct CAF subsets, with strengthened pro-angiogenic and pro-fibrotic cues. We derived and validated an 87-gene multicellular palmitoylation signature for risk stratification, and higher scores were consistently associated with adverse outcomes in external cohorts. Drug-response modelling highlighted vulnerabilities involving the HSP90-PI3K/MAPK axis. Functional assays and xenografts confirmed SH3BGRL as a key driver within this poor-prognosis programme. - Source: PubMed
Publication date: 2026/03/07
Xu JunHu YouQiao QiaoLu YongdaCen FanHou ShuoshuoYang HongbaoLv JianQin YanXia Suhua - Cellular actin dynamics are tightly regulated by actin-binding proteins with specialized domains. Here, we identify SH3BGRL proteins as modulators of actin dynamics, characterized by their thioredoxin (Trx) fold and the absence of the canonical enzymatic site. The Trx fold is generally associated with enzymatic activity; however, in this context, it functions non-enzymatically to enhance actin nucleation, inhibit depolymerization and cap the growing pointed end of the actin filament. Our results indicate that all SH3BGRL isoforms weakly promote actin nucleation in vitro by stabilizing energetically unstable actin dimers and trimers. Using molecular dynamics simulations and assays that directly probe the pointed end of the actin filament, we show that SH3BGRL proteins efficiently inhibit actin subunit addition at the pointed end by direct association with the terminal actin subunits. However, SH3BGRL proteins are less effective at preventing subunit loss from the pointed end, but they can cooperate with tropomodulin to enhance this activity in an isoform-specific manner, indicating that all isoforms are capable of forming a tripartite complex with actin and tropomodulin. Based on our results, we propose a new and more appropriate name that reflects the function of the SH3BGRL protein family: thioredoxin fold-containing pointed end capping proteins (TPECs). - Source: PubMed
Publication date: 2026/01/21
Heiringhoff Robin SMarke DanielCurth UteGreve Johannes N - In this study, we show that two fungal proteins, Aip5 (related to vertebrate SH3BGRL) and Bud6, directly interact to form a novel "composite nucleator," in which the pointed end of a nascent actin seed is bound by the thioredoxin-related domain of Aip5. The Aip5-Bud6 complex assembles F-actin seeds with free barbed ends and recruits formins to processively elongate and protect these ends from capping protein. The nucleation activities of Aip5 and Bud6 are critical for maintaining proper thickness of actin cable bundles in vivo, which prevents premature cable detachment from the bud neck and secretory traffic defects, as revealed by live imaging. In vitro single-molecule imaging reveals that after actin nucleation, Aip5 remains associated with a pointed end of the filament, and in vivo Aip5 puncta are observed directionally streaming inward from polarity sites by actin cable retrograde flow. Our findings expand the known diversity of actin nucleation mechanisms and reveal that Aip5 functions as a pointed-end capper in vivo. - Source: PubMed
Publication date: 2025/10/09
Magliozzi Joseph ORunyan Lucas AWelsh AdahPadrick Shae BGoode Bruce L - Previously, we identified that mutant p53 expression in cancer cells promotes engulfment of neighbouring cancer cells to form cell-in-cell (CIC) structures. This process gave mutant p53 cells an advantage in tumour formation in mouse xenograft experiments. TP53 can be found mutated at nearly every amino acid in cancers and mutant p53 expression is associated with various GOF (Gain-of-function) processes, including cancer cell invasion, metastasis, stemness and drug resistance. In the current manuscript, we identified SH3BGRL (Src homology 3 binding glutamate rich protein like) as a mutant p53-regulated gene and investigated to what extent SH3BGRL expression and cell engulfment are responsible for mutant p53-dependent anchorage-independent growth and chemoresistance. We demonstrate that mutant p53 expression drives cell engulfment in which the mutant p53 host cell moves in the direction of the target internal cell to form CIC structures. This is therefore more reminiscent of cell engulfment rather than cell entosis, in which cells invade into host cells. Using NGS (Next Generation Sequencing), we identified novel target genes of mutant p53 and demonstrate that cell engulfment requires SH3BGRL expression. We generated mutant p53 and p53 KO cell lines that stably overexpressed SH3BGRL and determined that SH3BGRL promotes etoposide resistance in mutant p53 cells and anchorage-independent growth independent of mutant p53 expression. Through FACS sorting of pure cell engulfing (CIC) populations, we could also show that engulfing cells have an enhanced etoposide resistance. These data suggest that SH3BGRL and cell engulfment are required for certain GOFs of mutant p53. - Source: PubMed
Publication date: 2025/07/01
Dolma LobsangPatterson Mary IBanyard AntoniaHall CallumBell StevenBreitwieser WolfgangSahoo SudhakarWeightman JohnGil Maria PazosAshton GarryBehan CaronFullard NicolaWilliams Lewis DMuller Patricia Aj - Acute myeloid leukemia (AML) is a fatal malignancy with rising incidence and low cure rates. This study aims to investigate the effect of alkB homolog 5 (ALKBH5)-mediated N6-methyladenosine (m6A) modification on adriamycin (ADR) resistance in AML. First, the levels of ALKBH5, taurine upregulated 1 (TUG1), YTH N6-methyladenosine RNA binding protein F2 (YTHDF2), euchromatic histone lysine methyltransferase 2 (EHMT2), and SH3 domain-binding glutamate-rich protein-like (SH3BGRL) were measured. IC50 values, cell proliferation, and apoptosis were determined. m6A levels were analyzed, and the binding interactions between TUG1 and YTHDF2, as well as TUG1 and EHMT2, were assessed. The stability of TUG1 and the enrichment of EHMT2 and H3K9me2 on the SH3BGRL promoter were confirmed. In vivo experiments were conducted to further validate the results. The findings revealed that ALKBH5 was overexpressed in both AML- and ADR-resistant cells, and silencing ALKBH5 reduced the ADR resistance of AML cells. ALKBH5 removed m6A modifications from TUG1, disrupting the interaction between YTHDF2 and TUG1, thereby stabilizing TUG1 expression. TUG1 bound to EHMT2, promoting H3K9me2 modification on the SH3BGRL promoter and suppressing SH3BGRL expression. Overexpression of TUG1 or knockdown of SH3BGRL reversed the suppressive effect of ALKBH5 knockdown on ADR resistance. In vivo, ALKBH5 knockdown inhibited ADR resistance in AML cells. In conclusion, ALKBH5 removed m6A modification to stabilize TUG1 expression in a YTHDF2-dependent manner, enhancing H3K9me2 levels on the SH3BGRL promoter and suppressing SH3BGRL expression, thus promoting ADR resistance in AML cells. - Source: PubMed
Publication date: 2025/04/03
Liu YonghuaJiang JinhongZeng YuxiaoJiang Yu