Ask about this productRelated genes to: SPPL2B antibody
- Gene:
- SPPL2B NIH gene
- Name:
- signal peptide peptidase like 2B
- Previous symbol:
- -
- Synonyms:
- IMP4, PSL1, KIAA1532
- Chromosome:
- 19p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2012-02-21
- Date modifiied:
- 2012-02-21
Related products to: SPPL2B antibody
Related articles to: SPPL2B antibody
- BACKGROUND: This study investigates HDAC3 as a potential immunotherapy biomarker in advanced non-small cell lung cancer (aNSCLC), focusing on its association with treatment response to immune checkpoint inhibitors (ICIs). METHODS: We employed a multi-phase approach in 78 aNSCLC patients with 138 plasma samples, starting with a discovery phase that identified differential autoantibodies (AAbs) using proteomic analysis in responders and non-responders. In the validation phase, we assessed AAb levels at multiple time points. Additionally, immunohistochemistry and multiple immunofluorescence (n = 21) were used to validate HDAC3 expression in FFPE samples, single-cell RNA sequencing (n = 26) was performed to explore gene expression differences, cell and animal experiments were performed. RESULTS: We identified 127 differential AAbs, with five key AAbs (HDAC3, METTL21C, HSPB3, SPACA7, and SPPL2B) consistently linked to prognosis pre- and post-treatment (p < 0.05). A risk score model based on these AAbs effectively predicted progression-free survival. Furthermore, HDAC3 expression correlated with significant pathway enrichments and was associated with higher TGFβ1, PD-L1 infiltration and lower CD8+ T cells infiltration (p < 0.05). HDAC3 knockdown significantly inhibited cell proliferation, impaired colony formation, and induced G0/G1 phase arrest in lung cancer cells. Preclinical models demonstrated that RGFP966, an HDAC3 inhibitor, combined with anti–PD-1 therapy enhanced CD8+ T cell infiltration (p < 0.05). CONCLUSION: Our findings underscore HDAC3’s role as a biomarker for predicting ICI response in aNSCLC and suggest its potential as a therapeutic target, paving the way for future studies on HDAC3-targeted therapies to improve immunotherapy outcomes. CLINICAL TRIAL NUMBER: not applicable. - Source: PubMed
Publication date: 2025/06/12
Dai LiyuanHuang LilingLi LinTang LeShi YuankaiHan Xiaohong - Specialized intramembrane proteases, known as iCLiPs, regulate the processing of transmembrane proteins by releasing intracellular domains, which can function as transcriptional regulators. The signal peptide peptidase-like (SPPL) family of iCLiPs, particularly SPPL2b, has roles in immune regulation, neuronal function, and disease pathogenesis. In the brain, SPPL2b localizes mainly in the plasma membrane of neurons and microglia and is abundant in the cortex and hippocampus. Its known substrates regulate neuronal growth, inflammation, and synaptic function, and increased amounts of SPPL2b have been found in postmortem brain tissue from patients with Alzheimer's disease. In this review, we discuss the currently known roles of SPPL2b, its substrates, and its disease implications. Understanding the downstream effects of SPPL2b-cleaved substrates will provide clearer insights into the impact of SPPL2b on cellular homeostasis and disease, potentially leading to new therapeutic strategies. - Source: PubMed
Publication date: 2025/05/06
Badman JackParracino AntoniettaKumar RajnishTambaro Simone - Signal peptide peptidase-like (SPPL) proteases, members of the intramembrane aspartyl protease family, have attracted increased interest due to their involvement in immune cell differentiation and cellular glycan structure regulation. However, the enzymatic domain involved in substrate recognition remains enigmatic. Here we provide evidence that the N-terminal protease-associated (PA) domains of the SPPL2 subfamily are involved in substrate recognition and discrimination of substrates that differ slightly in their luminal/extracellular domain. Presence of the SPPL2c PA domain impairs SPPL2a/b mediated tumor necrosis factor α (TNFα) initial cleavage, kinetics, and processivity in cells and in vitro. In contrast, the SPPL2a PA domain enhances processing by SPPL2b. Additionally, we demonstrate non-canonical shedding activity of SPPL3 on full-length TNFα and that the ability for consecutive cleavage differs within the SPPL-family and is mainly based on the SPPL2a/b membrane spanning body. This provides the basis to finally understand the mechanistic differences of these homologous proteases. - Source: PubMed
Publication date: 2025/04/30
Schlosser ChristineSharrouf KindaPapadopoulou Alkmini AHaug-Kröper MartinaSingh SumanJohler MaximilianPettinger JonasHorn HenrikeKoch MarcoHoeppner SabineFluhrer Regina - S100A8/A9, an innate immune protein, significantly regulates inflammatory processes and immune responses. While S100A8/A9 has been linked to various diseases, its association with head and neck squamous cell carcinoma (HNSCC) remains unclear. - Source: PubMed
Publication date: 2024/11/15
Hu YihongHe MinhuiHan YuchengZeng LuMa ZiweiZou Xianqiong - The "epileptic heart" concept is emerging, but the causal relationship between epilepsy and atrial fibrillation (AF) remains unclarified. - Source: PubMed
Publication date: 2024/09/12
Zheng ZequnChen HaohaoChen YanbinTan Xuerui