Ask about this productRelated genes to: SKP2 antibody
- Gene:
- SKP2 NIH gene
- Name:
- S-phase kinase associated protein 2
- Previous symbol:
- -
- Synonyms:
- FBXL1, FBL1, p45
- Chromosome:
- 5p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1995-12-18
- Date modifiied:
- 2016-10-05
Related products to: SKP2 antibody
Related articles to: SKP2 antibody
- Skp2, the substrate-recognition component of the SCF ubiquitin ligase complex, has been widely implicated in oncogenesis across diverse malignancies, positioning it as a compelling therapeutic target. The protein-protein interaction interface of Skp1-Skp2 offers an effective intervention point, as disruption of this interaction can impair the ability of Skp2 to identify and bind to its downstream substrates. However, inhibiting this interface with small-molecule inhibitors poses considerable challenge. Here, we introduce peptide sequences through screening of a peptide pool to target the Skp1-Skp2 core interface. The screening identified four linear precursors, which were further conformationally restricted to increase affinity and conformational stability by deploying cysteine-mediated late-stage crosslinking. Biophysical and cellular analyses of these crosslinked peptides revealed candidate peptides, P2SS and P4SS, which bind effectively to the desired interface and reduce Skp2 protein expression. Skp2 reduction further attenuates p27 ubiquitination, leading to the accumulation of p27 and subsequent G0/G1 cell-cycle arrest, ultimately resulting in cell death. Collectively, our findings establish the potential of first-in-class peptides in targeting the Skp1-Skp2 interface for the treatment of cancers driven by Skp2. - Source: PubMed
Publication date: 2026/09/22
Tolani SimranTripathi Nitesh ManiAntil HimanshuGhosh SouravMitra DebarghyaBanerjee AnirbanKumar SushilBandyopadhyay AnupamKumar Ashutosh - Guanylate-binding protein 2 (GBP2) has been reported to be involved in the progression of various human malignancies, but its specific functions and underlying molecular mechanisms in pancreatic cancer remain poorly understood. - Source: PubMed
Publication date: 2026/08/17
Fang ShilinNie HaihangZhou JingkaiZhang YongxiLiu XiaopingGuo JianchunHong YuntianDing YangNing YumeiWang FanKe HengningFang JunWang Haizhou - Long non-coding RNA SNHG1 has been implicated in hepatocellular carcinoma progression; however, how endocrine signaling regulates SNHG1-mediated ubiquitin-dependent protein turnover remains incompletely understood. We investigated whether thyroid hormone receptor signaling suppresses HCC progression through the MYC-SNHG1-SKP2-p21 axis. SNHG1 was frequently upregulated in HCC tissues and associated with aggressive clinicopathological features and unfavorable outcomes. In tumor specimens from our clinical HCC cohort and TCGA-LIHC tumors, THRB expression was inversely associated with SNHG1 expression. In TCGA-LIHC, combined THRB-low/SNHG1-high expression was associated with poorer survival. Functionally, SNHG1 promoted HCC cell proliferation, sphere formation, and invasion, whereas SNHG1 depletion suppressed these phenotypes. Mechanistically, thyroid hormone receptor β activation suppressed MYC expression and reduced SNHG1 levels. Promoter reporter and ChIP-qPCR analyses showed that TRβ occupied the MYC promoter region and that T3 reduced MYC promoter activity. MYC restoration maintained higher SNHG1 expression under T3 treatment, supporting MYC as an intermediary linking TRβ activation to SNHG1 repression. SNHG1 enhanced SKP2 expression and SKP2 mRNA stability, at least partly through a miR-340-5p-associated post-transcriptional mechanism. Increased SKP2 promoted ubiquitin-mediated degradation of p21 without markedly altering CDKN1A mRNA expression. Conversely, SKP2 knockdown attenuated SNHG1-induced p21 ubiquitination, proliferation, and invasion, whereas SKP2 re-expression partially restored these phenotypes in SNHG1-depleted cells. In xenograft models, hyperthyroid conditions reduced tumor growth and SKP2 expression while increasing p21 protein levels, and SNHG1 overexpression partially reversed these effects. Collectively, these findings support a TH/TRβ-MYC-SNHG1-SKP2-p21 regulatory axis linking endocrine signaling to lncRNA-mediated control of ubiquitin-dependent protein stability in HCC. - Source: PubMed
Publication date: 2026/09/14
Chen Chih-JungLin Yang-HsiangHuang Wei-ChiehShen Chia-HsingWang Chun-IYeh Chau-TingLu I-TaLin Kwang-HueiChi Hsiang-Cheng - Excessive inflammatory responses are a primary driver of acute lung injury, yet the underlying molecular mechanisms remain incompletely understood. In this study, we identify SKP2, an E3 ubiquitin ligase, as a critical negative regulator of pulmonary inflammation during methicillin-resistant (MRSA) infection. Mechanistically, SKP2 promotes the degradation of its direct substrate p27 (p27), which functions as an activator of a noncanonical NF-κB signaling pathway. We further demonstrate that p27 facilitates the recruitment of p38 kinase to heterogeneous nuclear ribonucleoprotein-U (hnRNPU), leading to direct phosphorylation of the transcriptional repressor FOXN3 at serine residues 83 and 85. This dual phosphorylation event triggers subsequent proteasomal degradation of FOXN3, thereby relieving transcriptional repression and enabling NF-κB-driven activation of pro-inflammatory genes. In vivo, genetic ablation of worsens pulmonary inflammatory injury, elevates neutrophil infiltration, and significantly reduces survival in MRSA-infected mice, and these effects are greatly rescued by concurrent p27 depletion. Collectively, our findings uncover the SKP2-p27-FOXN3 axis as a pivotal regulatory module in pulmonary inflammation and suggest that targeting this axis may offer a promising therapeutic strategy for bacterial infection-induced lung injury. - Source: PubMed
Publication date: 2026/09/11
Yu JinjinHu XinghongWang HuanhuanYu JingyuJin LeleLi YingkeZhou JihongZhu XinxingMoses Emmanuel JairajZheng ChunfuZhang YongLi Wei - AKT (protein kinase B, PKB) coordinates the balance between anabolic and catabolic signaling in skeletal muscle through distinct ubiquitin chain types. Some E3 ubiquitin ligases (E3s) and deubiquitinases (DUBs) form stable binary complexes via non-catalytic interfaces, adding a regulatory layer unavailable to either enzyme alone. This mechanistic synthesis review presents a systematic literature analysis (inception to May 2026; 26 eligible studies). It identified four E3-DUB pairs proposed to regulate AKT in skeletal muscle. These are TRAF6-CYLD (plasma-membrane K63-ubiquitination), MUL1-USP9X (mitochondrial K48-ubiquitination of AKT2), CHIP-UCH37 (proteasome-proximal quality control), and SCF-Skp2-USP37 (PHLPP1/2-dependent control of AKT Ser473 phosphorylation). All four interfaces are structurally separate from the catalytic sites and are regulated by upstream kinase phosphorylation. Evidence for the four pairs is markedly uneven. TRAF6-CYLD is supported by endogenous co-immunoprecipitation and functional data in muscle models. CHIP and UCH37 each act on AKT-related substrates independently and are individually well documented, but a direct CHIP-UCH37 interaction has not itself been demonstrated. SCF-Skp2-USP37 interaction data rest on a real but non-muscle direct interaction, whereas MUL1-USP9X has no reported direct interaction at all; CHIP-UCH37, SCF-Skp2-USP37, and MUL1-USP9X are therefore all presented as testable hypotheses of varying strength. In chronic atrophy, available data are consistent with disruption of these complexes contributing to AKT suppression through parallel, largely independent mechanisms. However, simultaneous disruption of all four has not been demonstrated in a single system. Available gene expression and protein datasets from sarcopenic muscle broadly support these predictions, though direct experimental validation in human tissue remains pending. This complex-centric framework recasts AKT ubiquitination as an integrated regulatory framework. Each structurally autonomous interface may represent a potentially distinct target for muscle-wasting conditions that currently lack approved therapies. - Source: PubMed
Dabur Rajesh