SKP2
- Known as:
- SKP2
- Catalog number:
- 000226A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- SKP2
Related genes to: SKP2
- 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
Related articles to: SKP2
- Philadelphia chromosome-positive (Ph) leukemia is among the most aggressive forms of leukemia and arises from the Philadelphia chromosome (Bcr-Abl fusion gene) abnormality. This disease is associated with a poor prognosis in adults and resistance to traditional treatment. Thus, the identification of novel therapeutic targets and drugs for Ph leukemia remains crucial. S-phase kinase-associated protein 2 (Skp2), a key component of the SCF ubiquitin ligase complex, is aberrantly overexpressed in various malignancies and therefore represents a potential target for anticancer therapy. This study aimed to elucidate the therapeutic mechanism of action of AAA-237, a novel Skp2 inhibitor, in Ph + leukaemia. Cellular responses to AAA-237 were evaluated using cell viability, EdU incorporation, and colony formation assays. Pyroptosis was observed by scanning electron microscopy (SEM), immunofluorescence, lactate dehydrogenase (LDH) detection, ELISA, and Western blotting. Phospholipid metabolism was evaluated through metabolomic profiling and RNA sequencing. Mechanistic findings were validated using Western blotting and quantitative real-time PCR. Mitochondrial and endoplasmic reticulum damage were evaluated using Ca, ATP, TMRM, and mitochondrial reactive oxygen species (ROS) assays. In vivo efficacy and safety of AAA-237 were examined in a xenograft model. The results showed that AAA-237 targeted Skp2 and inhibited Bcr-Abl phosphorylation and ubiquitination, suppressing the proliferation of Ph leukemia cells in a concentration-dependent manner at the cellular level. AAA-237 induced both pyroptosis and apoptosis through caspase-dependent mechanisms. Treatment with AAA-237 inhibited the PI3K/AKT signaling pathway and disrupted phospholipid metabolism, resulting in dysregulated phospholipid metabolism. AAA-237 also increased PACS2 expression, remodeled mitochondria-associated endoplasmic reticulum membranes (MAMs), and induced mitochondrial dysfunction and endoplasmic reticulum damage. In vivo, AAA-237 effectively suppressed leukemia progression. These results show that AAA-237, a novel Skp2 inhibitor, inhibits the proliferation of Ph leukemia cells by reducing Bcr-Abl phosphorylation and ubiquitination. AAA-237 further induces caspase-dependent pyroptosis and apoptosis by disrupting phospholipid metabolism and impairing MAM homeostasis. These results provide preliminary experimental evidence supporting the development of targeted candidate therapeutics for Ph leukemia. - Source: PubMed
Publication date: 2026/08/24
Tian XiaolongLi JiarunYang GuancuiJiang PeijieYang XueqingYang ShijieZhang XiLiu Jinyi - Breast cancer is the most prevalent and lethal cancer among women worldwide. Although classification based on ERα, PR, and HER2 status guides treatment decisions, misclassification remains a challenge due to the complexity of ERα-associated transcriptional network. Identifying biomarkers that better reflect ERα activity may improve tumor stratification and therapeutic decision-making. We hypothesized that an ERα-related transcriptional framework could improve molecular characterization of breast cancer subtypes. - Source: PubMed
Publication date: 2026/08/05
Dozal-Luna Ana JazmínSantuario-Facio Sandra KCardona-Huerta ServandoGómez-Macías Gabriela SofíaRangel-Escareno ClaudiaLira-Albarrán SaúlGómez-Flores-Ramos LilianaOrtiz-López Rocío - Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with limited treatment options, particularly in advanced stages. Immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, and CTLA-4 have shown promise in cancer immunotherapy, but response rates in HCC remain variable. - Source: PubMed
Khodarahmi MasoudAmiri Manjili DanialYarahmadi ForoozanMokhtari TahereDashtizadeh AdibRajabi Dezfooli HeliaMonirvaghefi KhaterehsadatGharedaghi HosseinDolatshahi SinaHasanabadi ZahraMoammer FarzanehMobinikhaledi MahyaYavari Kondori AidaFarajpour ZahraKondori Varnosfaderani PardisHashemi ZahraMahdizadeh Mohammad AminBehfar QumarsSandoghchian Shotorbani SiamakSargazi Moghaddam Nasibeh - The progressive loss of midbrain dopamine neurons leading to motor deficits is the primary cause of Parkinson's disease (PD). Emerging reports on the role of NURR1 in the differentiation and maintenance of dopamine neurons; the association of reduced levels/familial mutants of NURR1 in PD subjects makes it a promising candidate for developing novel therapeutics. In the present study, while examining the effects of known deubiquitinase inhibitors, we have identified that the USP10/13 inhibitor, spautin-1, upregulated NURR1 levels in a transcription-dependent manner. Further, USP13, but not USP10, was found to be essential in spautin-1-mediated NURR1 regulation. Reports indicate that USP13 deubiquitinates SKP2 and thereby prevents it from degradation. Also, SKP2 is an E3 ligase for P57/kip2 and reduced SKP2 expression leads to enhanced P57/kip2 levels. In line with the above findings, cells treated with spautin-1 exhibited reduced SKP2 with a concomitant increase in P57/kip2 levels. Our results indicate that spautin-1-mediated regulation of the USP13-SKP2-P57/kip2 axis could play a crucial role in NURR1 upregulation since overexpression of SKP2, or knockdown of P57/kip2, abrogated spautin-1-mediated effects. Further, spautin-1 mediated neurite outgrowth of dopaminergic cells was mitigated under NURR1 knockdown conditions, indicating that small molecule activators of NURR1 could promote neurite outgrowth. Lastly, the ability of spautin-1 in enhancing tyrosine hydroxylase staining in vivo in PD mouse model suggests that pharmacological activation of NURR1 could mitigate biochemical manifestations of PD. - Source: PubMed
Publication date: 2026/08/12
Edward AnnaPuttapaka Srinivas NVulli AravindKalivendi Shasi V - The ubiquitin-proteasome system (UPS) plays a central role in regulating protein homeostasis and degradation. Its dysregulation is closely associated with various diseases, including cancer. S-phase kinase-associated protein 2 (SKP2) is a key E3 ubiquitin ligase component of the UPS. It induces proteasome-mediated protein degradation or modulates substrate function by conjugating K48-linked or K63-linked ubiquitin chains to diverse target proteins. Recent studies have shown that the overexpression of SKP2 in several cancer types is correlated with poor clinical outcomes, underscoring its potential as a therapeutic target. Notably, emerging evidence has expanded the functional repertoire of SKP2 beyond cell cycle control to encompass metabolism, DNA repair, stemness, tumor microenvironment (TME) and immunotherapy response, positioning it as an increasingly attractive target for intervention. In this review, the oncogenic properties of SKP2 and its underlying mechanisms were elucidated in multiple cancer types. Moreover, we systematically summarized future directions for SKP2-targeted therapy. - Source: PubMed
Publication date: 2026/08/07
Zheng Sheng-AnWang ChengYao Xiao-DieSheng Jia-JiaLiu Po-WuWang YingDeng Shi-JiaLi He