WSB2 (WD Repeat And SOCS Box Containing 2)

WSB2 and COMMD2 jointly predicted that hsa-miR-185-5p, hsa-miR-4644 and hsa-miR-4306 were the common microRNAs (miRNAs) and regulatory networks. This study successfully established a neddylation-associated prognostic risk model for LSCC and revealed that COMMD2, WSB2, and CUL9 could act as new therapeutic targets, which might provide valuable information for the research and treatment of LSCC.

While Wsb2 is not essential in most cells, it is essential in cells derived from tumors of the nervous system, and knockdown of Wsb2 in these lines causes death by apoptosis. This work uncovers a novel mechanism of apoptosis regulation, with implications for developing therapies against neuroblastomas and other cancers reliant on this pathway for survival.

Furthermore, the expression of NUPR1 (encoding nuclear protein 1, transcriptional regulator), LDLRAD4 (encoding low density lipoprotein receptor class A domain containing 4) and MDM2 (encoding mouse double min 2) were verified by RT‑qPCR. Overall, the present study contributes to the understanding of the carcinogenic role of WSB2 in different types of cancer.

Although inhibitors targeting BCL-2, such as Venetoclax, have shown efficacy in hematological malignancies, their therapeutic potential in solid tumors remains limited...These findings identify WSB2 as a critical regulator of mitochondrial apoptosis and reveal the dysregulation of the WSB2-NOXA axis as a key factor contributing to apoptosis resistance in cancer cells. Targeting both WSB2 and anti-apoptotic BCL-2 family proteins holds promising therapeutic potential for overcoming resistance in human cancers.

Our recent work demonstrates that WSB1 and WSB2 (WSB1/2), two additional SOCS-box proteins with structurally similar WD40 repeat domains, function as substrate-recognizing subunits of ECSWSB1/2 to specifically mediate the ubiquitination and degradation of chromatin-associated RelA methylated at Lys314/315. In this review, we summarize the discovery and functional importance of ECSSOCS1 and ECSWSB1/2 in terminating NF-κB activity, highlight the distinct molecular mechanisms by which they ubiquitinate chromatin-associated RelA in a modification- and gene-specific manner, and discuss their potential as therapeutic targets for inflammatory diseases and cancer.

The ubiquitination degradation of KLF15 was mediated by WSB2, which led to transcriptional repression of PDLIM2 and further activation of the NF-κB pathway, ultimately promoting HCC lipogenesis and development.

Targeting mTOR with everolimus, an oral drug, significantly blocked WSB2-triggered HCC tumorigenesis and metastasis in vivo. In clinical samples, high expression of WSB2 was associated with low wild-type p53 expression and high p-mTOR expression. These findings demonstrate that WSB2 is overexpressed and degrades wild-type p53 and then activates the IGFBP3-AKT/mTOR axis, leading to HCC tumorigenesis and lung metastasis, which indicates that targeting mTOR could be a new therapeutic strategy for HCC patients with high WSB2 expression and wild-type p53.

These E3 ligases also control cell cycle progression and cell proliferation through regulation of cyclin D1 protein stability. Our study provides novel insights into the regulatory mechanisms of cyclin D1 protein stability and function.

Histone methylation is rising as an important factor affecting tumorigenicity and tumor progression. Our findings verified the significance of RBBP5-mediated H3K4 modification in melanoma and the potential regulatory mechanisms of melanoma proliferation and growth, suggesting that RBBP5 is a potential therapeutic target for the treatment of melanoma.