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GENE:

WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2)

News alerts, weekly reports and conference planners

Palmitoylation modification of SPI1 promotes nasopharyngeal carcinoma radioresistance through inhibiting c-CBL-mediated ubiquitination and degradation. (PubMed, Drug Resist Updat)

Collectively, our findings suggest that SPI1 palmitoylation inhibits c-CBL-mediated ubiquitination and degradation, thereby enhancing SPI1 protein stability and its transcriptional regulation of miR-205-5p. Upregulated miR-205-5p in NPC cells is packaged into exosomes and transferred to endothelial cells, where it targets and inhibits WWC2 expression, eventually promoting angiogenesis and NPC radioresistance.

8 days ago

Journal

SPI1 (Spi-1 Proto-Oncogene) • WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2) • MIR205 (MicroRNA 205)

29d

Targeting the WWP2-ASPP2 axis overcomes cisplatin resistance by inhibiting the mevalonate pathway in TP53-mutant bladder cancer. (PubMed, Int J Biol Macromol)

Overall, the WWP2-ASPP2-MVA pathway axis is identified as a novel driver of cisplatin resistance in bladder cancer. These results establish a mechanistic basis for targeting this axis to restore chemosensitivity, offering a promising therapeutic strategy for recalcitrant disease.

29 days ago

Journal

WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2)

TP53 mutation

cisplatin

2ms

Exosomal SNHG26 mediates immunosuppression by impairing NK cells in tongue cancer. (PubMed, NPJ Precis Oncol)

SNHG26 depletion reversed NK cell suppression and cisplatin resistance in vitro and in vivo. Thus, our study identifies exosomal SNHG26 as a key mediator of cisplatin resistance and NK cell dysfunction in TSCC, suggesting its potential as a promising therapeutic target.

2 months ago

Journal

IL2 (Interleukin 2) • SOX2 • HLA-DRA (Major Histocompatibility Complex, Class II, DR Alpha) • TGFB1 (Transforming Growth Factor Beta 1) • WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2)

cisplatin

2ms

WWP2-induced inhibition of hepatocellular carcinoma cellular senescence via the ubiquitination and degradation of p21. (PubMed, Cell Death Dis)

This functional interplay was corroborated in vivo, as WWP2 depletion enhanced tumor cell senescence and suppressed tumor growth, an effect that was partially rescued by concurrent CMTM6 knockdown. Taken together, our findings establish the WWP2-CMTM6-p21 axis as a pivotal regulatory mechanism of cellular senescence in HCC and shed new light on senescence-related therapeutic strategies for HCC.

2 months ago

Journal

CMTM6 (CKLF Like MARVEL Transmembrane Domain Containing 6) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2)

3ms

LAPTM4B Confers Resistance to EGFR-TKIs by Suppressing the Proteasomal Degradation of ATP1A1 in Non-small Cell Lung Cancer. (PubMed, Int J Biol Sci)

In this study, we found that EGFR-TKI, including gefitinib and osimertinib, impaired WWP2-mediated proteasomal degradation of LAPTM4B. These compounds synergistically enhance the efficacy of EGFR-TKIs in NSCLC models in vitro and in vivo, with minimal toxicity. Integrative analyses of patient tissue samples, cellular models, an animal model, and cancer databases highlight the critical role of the LAPTM4B-ATP1A1-lysosomal acidification axis in EGFR-TKI resistance, providing a promising therapeutic avenue for overcoming resistance in EGFR-mutant NSCLC.

3 months ago

Journal

WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2) • ATP1A1 (ATPase Na+/K+ Transporting Subunit Alpha 1)

EGFR mutation

Tagrisso (osimertinib) • gefitinib

3ms

FAM189A2 activates Hippo signaling pathway by abrogating WWP2-mediated LATS1 ubiquitination, to inhibit the glycolysis and proliferation processes of lung adenocarcinoma. (PubMed, J Transl Med)

FAM189A2 can be considered as a potential diagnostic and prognostic marker associated with LUAD, and suppresses the proliferation and glycolytic metabolism of LUAD cells via WWP2-LATS1-YAP signaling, which will provide a corresponding theoretical foundation for the development of small molecule inhibitors.

3 months ago

Journal

LATS1 (Large Tumor Suppressor Kinase 1) • WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2)

Visudyne (verteporfin)

6ms

Paraspeckle protein NONO regulates active chromatin by allosterically stimulating NSD1. (PubMed, Cell Rep)

Mouse embryonic stem cells engineered with mutations in the aromatic pocket of NSD1-PWWP2 cannot differentiate into neural progenitor cells, and genetic depletion of NONO partially phenocopies this defect, potentially explaining the neurodevelopmental disorder phenotypes in NSD1- and NONO-deficient diseases. Our work uncovers a mechanism driving active chromatin domain formation, an implication in the interplay between nuclear paraspeckles and active chromatin, and a vulnerability of NSD1 for therapeutic interventions.

6 months ago

Journal

NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2)

7ms

TNFAIP2 deficiency drives formation of an immunosuppressive tumor microenvironment and confers resistance to anti-PD-1 therapy in skin cutaneous melanoma. (PubMed, Sci Rep)

Moreover, TNFAIP2 overexpression clearly increased the sensitivity of SKCM to anti-PD-1 immunotherapy. The above results indicate the tumor-suppressive role of TNFAIP2, which may be a promising target for improving the efficacy of ICB treatment in SKCM.

7 months ago

Journal • PD(L)-1 Biomarker • IO biomarker

CD8 (cluster of differentiation 8) • TNFA (Tumor Necrosis Factor-Alpha) • WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2)

8ms

circGIGYF1 inhibits stemness and metastasis in colorectal cancer by promoting WWP2-HOXD13 interaction to regulate β-catenin signalling. (PubMed, Commun Biol)

Importantly, circGIGYF1 overexpression or HOXD13 knockdown significantly reduces tumor growth and liver metastasis in mouse models. These findings reveal a circGIGYF1/WWP2/HOXD13/β-catenin regulatory axis in CRC progression and highlight circGIGYF1 as a potential therapeutic target for developing strategies to combat CRC metastasis and recurrence.

8 months ago

Journal

WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2)

8ms

Endothelial cells-derived SEMA3G suppresses glioblastoma stem cells by inducing c-Myc degradation. (PubMed, Cell Death Differ)

These findings illustrate that ECs play an intrinsic inhibitory role in GSCs stemness via the SMEA3G-c-Myc distal regulation paradigm. Targeting SEMA3G signaling may have promising therapeutic benefits for GBM patients.

8 months ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CDC42 (Cell Division Cycle 42) • WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2) • SEMA3G (Semaphorin 3G)

8ms

HECW2 knockdown suppresses the development of infantile hemangioma by inhibiting ALKBH5/LDHA axis-mediated glycolysis. (PubMed, Am J Cancer Res)

Additionally, in vivo validation using an IH xenograft mouse model demonstrated that HECW2 knockdown significantly suppressed tumor growth. These findings established HECW2 as a key regulator in IH progression through the regulation of ALKBH5/LDHA-mediated glycolysis, suggesting its potential as a therapeutic target for IH treatment.

8 months ago

Journal

LDHA (Lactate dehydrogenase A) • WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2) • ALKBH5 (AlkB Homolog 5, RNA Demethylase) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)

10ms

Ubiquitin-proteasome Pathway-linked Gene Signatures as Prognostic Indicators in Prostate Cancer. (PubMed, Anticancer Res)

The identified gene subset provides novel prognostic insights into PCa progression and survival. These findings highlight potential biomarkers and therapeutic targets within the ubiquitin-proteasome pathway, offering new avenues for personalized treatment strategies.

10 months ago

Journal • Gene Signature • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • CDH1 (Cadherin 1) • MALT1 (MALT1 Paracaspase) • SOCS1 (Suppressor Of Cytokine Signaling 1) • DDB1 (Damage Specific DNA Binding Protein 1) • CDC20 (Cell Division Cycle 20) • OASL (2'-5'-Oligoadenylate Synthetase Like) • PIAS4 (Protein Inhibitor Of Activated STAT 4) • UBE2H (Ubiquitin Conjugating Enzyme E2 H) • UHRF1 (Ubiquitin Like With PHD And Ring Finger Domains 1) • WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2) • IKBKB (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Beta) • UBE2C (Ubiquitin Conjugating Enzyme E2 C) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5) • CD3E (CD3 Epsilon Subunit Of T-Cell Receptor Complex) • NEDD4 (NEDD4 E3 Ubiquitin Protein Ligase) • STIP1 (Stress Induced Phosphoprotein 1)