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
- 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 - Rho related BTB domain containing 1 (RhoBTB1) is highly expressed in placenta and functions to deliver protein targets to the Cullin-3 (CUL3) E3 ubiquitin ligase where they are targeted for ubiquitination and degradation. The targets of RhoBTB1 in placenta have not been identified. Using RNAscope, we show that RhoBTB1 is mainly expressed in syncytiotrophoblasts (SCT) in the human and mouse placenta. We employed ascorbate peroxidase 2-mediated targeted proteomics to identify RhoBTB1 binding proteins in immortalized human extravillous trophoblast (HTR8/SVneo) cells. We selected 9 RhoBTB1-interacting proteins to examine functionally. Two of these, S-Phase Kinase Associated Protein 2 (SKP2) and Rho GTPase-Activating Protein 29 (ArhGAP29), increased in abundance when Cullin activity was blocked by the neddylation inhibitor MLN4924 and co-immunoprecipitated with RhoBTB1. SKP2 increased in abundance in CRISPR-Cas9 HEK293 cells that lack CUL3, and in HTR8/SVneo cells after siRNA-mediated inhibition of RhoBTB1. SKP2 was ubiquitinated by a RhoBTB1- and CUL3-dependent mechanism providing evidence that its stability is regulated by RhoBTB1/CUL3. Like RhoBTB1, SKP2 is highly expressed in the placenta. Reanalysis of single cell RNA sequencing data sets revealed that SKP2 exhibits co-expression with RhoBTB1 in SCT precursor cells, SCTs, and cytotrophoblasts. These findings identify SKP2 as a RhoBTB1/CUL3 target in the placenta. - Source: PubMed
Tvina Alina LLivergood M ChristineKumar GauravHole Valerie WOpichka Megan AIrizarry Luisangeli MunizLu Ko-TingWackman Kelsey KGrobe Justin LNakagawa PabloMcIntosh Jennifer JSigmund Curt D - Genetic inactivation of SKP2 has been shown to effectively prevent cancer initiation and block tumorigenesis. However, direct in vivo evidence for SKP2 on cancer initiation and prostatic microenvironment is still lacking and a SKP2 humanized mouse model is critical for developing prostate cancer immunoprevention approaches through targeting SKP2. We therefore have established a prostate-specific human SKP2 knock-in mouse model driven by an endogenous mouse probasin promoter. Overexpression of hSKP2 induces PIN and low-grade carcinoma. RNA-sequencing analysis revealed significant gene expression alterations in EMT, extracellular matrix, and interferon signaling. Single-cell deconvolution showed an increase of fibroblast population and a decrease of CD8 T cell and B cell populations. Consistent with these results from the SKP2 humanized mouse, SKP2 protein is overexpressed in human prostatic hyperplasia, PIN and prostate adenocarcinoma compared to normal prostate tissues. Overexpression of SKP2 markedly increased cell migration and invasion and induced the gene expression of EMT and interferon pathways. Inhibition of SKP2 signaling by Flavokawain A and C1 reverses EMT and affects EMT and interferon-related gene expression. In addition, paired prostate organoids were derived from SKP2 humanized and wild-type mice for drug screening and validated by known SKP2 inhibitors, Flavokawain A and C1. Both of which selectively decreased viability and altered the morphologies of organoids of hSKP2 knock-in rather than wild-type mice. Our studies provide a well-characterized prostate-specific hSKP2 knock-in mouse model and offer new mechanistic insights for understanding the oncogenic role of SKP2 in shaping the prostatic microenvironment during early carcinogenesis. - Source: PubMed
Publication date: 2026/08/01
Song LiankunSong YurongNguyen VyvyanXu ShanHo KellyMohammed AltafShoemaker Robert HHoang Bang HYu JianhuaUchio EdwardZi Xiaolin - Kidney renal clear cell carcinoma (KIRC) is the most common subtype of renal cell carcinoma, accounting for 75-80% of cases. Although Prohibitin 1 () has been implicated in tumorigenesis, its role in KIRC remains unclear. This study aimed to investigate the expression, function, and underlying mechanisms of in KIRC. - Source: PubMed
Cao ChenbinQi HeXiang LuZhu WenshuaiShi YuxuanMa XiaoliWang YunshanJia YanfeiXing Yuanxin