Ask about this productRelated genes to: WSB1 antibody
- Gene:
- WSB1 NIH gene
- Name:
- WD repeat and SOCS box containing 1
- Previous symbol:
- -
- Synonyms:
- DKFZp564A122, DKFZp564B0482, SWIP1
- Chromosome:
- 17q11.1
- Locus Type:
- gene with protein product
- Date approved:
- 2004-02-20
- Date modifiied:
- 2016-10-05
Related products to: WSB1 antibody
Related articles to: WSB1 antibody
- Tumor-infiltrating lymphocytes (TIL) often fail to restrain tumor growth due to progressive differentiation into an "exhausted" state. Tissue-resident memory T cells (T) maintain protection from infection for years in healthy tissues, and patient tumors that contain TIL with T features are associated with better prognosis. Proteomic and transcriptomic profiling of T cell populations identified proteostasis as a significant factor distinguishing T and progenitor-exhausted TIL from terminally exhausted TIL, including loss of E3 ubiquitin ligases NEURL3, RNF149, and WSB1, with accumulation of unfolded proteins despite functional proteasome activity. Enforced expression of these ligases in T cells preserved stem-like TCF1 populations and improved function in tumors and chronic infection, whereas deficiency impaired TIL and altered T cell differentiation during acute infection. Sustained ligase expression rescued the accumulation of unfolded proteins in TIL and improved immunotherapy outcomes in preclinical models, underscoring the critical role of proteostasis in TIL function and highlighting a promising avenue for advancing cancer immunotherapy. - Source: PubMed
Publication date: 2026/04/29
Scharping Nicole EGe XuezhenMatias Maria InêsJiang FulinCafferata AllisonHeeg MaximilianMonell AlexanderGalletti GiovanniCheung Kitty PRock AngelicaThao NickShuttleworth Sydnye LBauer Michael ATakehara Kennidy KFerry AmirQuon SaraKoss BrianMyers Samuel ABennett Eric JGoldrath Ananda W - Tumor-infiltrating lymphocytes (TIL) often fail to restrain tumor growth due to progressive differentiation to an 'exhausted' state. In healthy tissues, tissue-resident memory T cells (T) maintain protection for years, and patient tumors that contain TIL with T features are associated with better prognosis. Proteomic and transcriptomic profiling of T cell populations identified proteostasis as a significant factor distinguishing T and progenitor-exhausted TIL from terminally-exhausted TIL, including loss of E3 ubiquitin ligases NEURL3, RNF149, and WSB1, with accumulation of unfolded proteins in spite of functional proteasome activity. Enforced expression of these ligases by TIL preserved stem-like TCF1 populations and improved antitumor function, whereas their knockout impaired TIL and altered T cell differentiation in acute infection. Sustained ligase expression rescued accumulation of unfolded proteins in TIL and improved immunotherapy outcome in preclinical models, highlighting the critical role of proteostasis in TIL function and identifying new avenues for advancing cancer immunotherapy. - Source: PubMed
Publication date: 2026/02/10
Scharping Nicole EGe XuezhenMatias Maria InêsJiang FulinCafferata AllisonHeeg MaximilianMonell AlexanderGalletti GiovanniCheung Kitty PRock AngelicaThao NickShuttleworth Sydnye LBauer Michael ATakehara Kennidy KFerry AmirQuon SaraKoss BrianMyers Samuel ABennett Eric JGoldrath Ananda W - Targeted protein degradation is a promising strategy for addressing oncogenic drivers that are difficult to inhibit with small molecules, such as KRAS. While bioPROTACs expand the range of targetable proteins, their clinical translation is limited by inefficient delivery. To overcome this barrier, we engineered a chimeric protein, termed DEG-KRAS, which consists of a KRAS-binding domain derived from CRAF (RBD/CRD), an E3 adaptor (WSB1), and an optional trafficking module. DEG-KRAS induced degradation of active KRAS and suppressed proliferation in pancreatic cancer cell lines by reducing phospho-ERK levels. Notably, DEG-KRAS expression in mesenchymal stem cells (MSCs) exerted a bystander effect, leading to KRAS degradation and growth inhibition in co-cultured cancer cells. Specificity was confirmed using control constructs lacking each functional domain. Although the antiproliferative effect was modest compared to direct expression in cancer cells, the indirect impact highlights a non-cell-autonomous mechanism. While the precise mode of intercellular transfer remains to be elucidated, these findings suggest the involvement of extracellular vehicles or other secretory pathways. This strategy may offer a novel therapeutic avenue for targeting KRAS-driven tumors, particularly pancreatic adenocarcinoma. - Source: PubMed
Publication date: 2025/11/01
Inano ShojiroTakaori-Kondo AkifumiNakajima Takako - Polyubiquitination plays a critical role in tumor biology, yet its significance in prostate cancer remains incompletely understood. Here, we investigated the expression and function of SOCS-box E3 ligases in prostate cancer. Analysis of TCGA data revealed WSB1 overexpression, which correlated with advanced pathological stage, high Gleason score, and poor prognosis. Functional assays demonstrated that WSB1 knockdown suppressed prostate cancer cell proliferation, colony formation, and migration in vitro, and inhibited tumor growth and Ki67 expression in vivo. Mechanistically, mass spectrometry and co-immunoprecipitation identified ISOC2 as a key WSB1 interactor. WSB1 stabilized ISOC2 by promoting its interaction with the deubiquitinase OTUD4, thereby preventing ISOC2 degradation via the ubiquitin-proteasome pathway. Silencing either ISOC2 or OTUD4 phenocopied the tumor-suppressive effects of WSB1 ablation. Importantly, disruption of the WSB1/OTUD4/ISOC2 axis upregulated P16INK4a expression, and co-silencing of P16INK4a partially restored tumorigenic properties. Our findings unveil a novel WSB1/OTUD4/ISOC2 signaling network that drives prostate cancer progression by modulating ubiquitin signaling and repressing P16INK4a, positioning WSB1 as a promising therapeutic target. - Source: PubMed
Publication date: 2025/10/25
Sun JianWang FeiFeng YuxuanQiu XiyaQu WenyingHe XuefengXie JianjunLi Gang - Metastasis represents the major cause of colorectal cancer (CRC)-related mortality. Here, we sought to examine the mechanism of WD repeat and SOCS box-containing protein 1 (WSB1), an E3 ubiquitin ligase, in CRC liver metastasis (LM). An orthotopic implantation CRC model was constructed to analyze the differences in gene expression within cecum xenograft tumors (CXTs) and LMs. WSB1 was significantly higher expressed within the LM of nude mice than CXT, whereas type II iodothyronine deiodinase (DIO2) was higher in CXT. WSB1 knockdown hampered LM in CRC with orthotopic tumors, which was reversed by DIO2 knockdown. WSB1 degraded DIO2 by ubiquitination modification. The roles of the WSB1/DIO2/T3/TRβ1 axis in CRC cell proliferation, migration, invasion, and stemness were also probed. Treatment of SW620 cells with knockdown of DIO2 in combination with T3 reversed the malignant progression of CRC in vitro and in vivo caused by knockdown of DIO2, but the intervention of sh-TRβ1 in turn reversed the therapeutic benefit of T3 on malignant progression of CRC. Taken together, our results identify the DIO2 degradation by WSB1 and subsequent impairment of T3/TRβ1 signaling as mechanisms leading to LM in CRC. These findings can inform therapeutic interventions for this event. - Source: PubMed
Publication date: 2025/10/17
Zhai PengLi QiangJiang YongjunZhang HuaguoXing Chungen