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S-phase kinase-associated protein 2

Skp2, F-box protein Skp2, S-phase kinase-associated protein 2
This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class; in addition to an F-box, this protein contains 10 tandem leucine-rich repeats. This protein is an essential element of the cyclin A-CDK2 S-phase kinase. It specifically recognizes phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also referred to as p27 or KIP1) predominantly in S phase and interacts with S-phase kinase-associated protein 1 (SKP1 or p19). In addition, this gene is established as a protooncogene causally involved in the pathogenesis of lymphomas. Alternative splicing of this gene generates three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2011] (from NCBI)
Top mentioned proteins: p27, PCNA, Ubiquitin, SCF, V1a
Papers on Skp2
Postponing the Hypoglycemic Response to Partial Hepatectomy Delays Mouse Liver Regeneration.
Rudnick et al., Saint Louis, United States. In Am J Pathol, Feb 2016
The regulation of specific liver regeneration-promoting signals, including hepatic induction of cyclin D1 and S-phase kinase-associated protein 2 expression and suppression of peroxisome proliferator-activated receptor γ and p27 expression, was also disrupted by dextrose infusion.
Genetic variants in cell cycle control pathway confer susceptibility to aggressive prostate carcinoma.
Daw et al., Saint Louis, United States. In Prostate, Jan 2016
RESULTS: Eleven variants within 10 genes (CCNC, CCND3, CCNG1, CCNT2, CDK6, MDM2, SKP2, WEE1, YWHAB, YWHAH) in the European-American population and nine variants in 7 genes (CCNG1, CDK2, CDK5, MDM2, RB1, SMAD3, TERF2) in the African-American population were found to be associated with aggressive PCa using at least one model.
A haploid genetic screen identifies the G1/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity.
van Vugt et al., Groningen, Netherlands. In Proc Natl Acad Sci U S A, Jan 2016
Insertion site mapping of cells that survived long-term Wee1 inhibition revealed enrichment of G1/S regulatory genes, including SKP2, CUL1, and CDK2.
Expression of Skp2 and p27(kip1) proteins in hypopharyngeal squamous cell carcinoma and its clinical significance.
Wu et al., Quanzhou, China. In Oncol Lett, Dec 2015
UNASSIGNED: The aim of the present study was to determine the effect of S-phase kinase-associated protein 2 (Skp2) and cyclin-dependent kinase inhibitor p27(kinase-interacting protein 1) (p27(kip1)) protein expression on the occurrence and development of hypopharyngeal squamous cell carcinoma.
Protein phosphatase 1 suppresses androgen receptor ubiquitylation and degradation.
Chen et al., Boston, United States. In Oncotarget, Dec 2015
Moreover, we find that the PP1α inhibitor tautomycin increases phosphorylation of AR ubiquitin ligases including SKP2 and MDM2 at sites that enhance their activity, providing a mechanism by which PP1α may suppress AR degradation.
The SCF-type E3 Ubiquitin Ligases as Cancer Targets.
Kitagawa et al., Hamamatsu, Japan. In Curr Cancer Drug Targets, Dec 2015
S-phase kinase-associated protein 2 (SKP2) (also known as FBXL1) is often overexpressed in human cancers, and functions as an oncogenic E3 ligase to degrade tumor suppressor gene products.
p27(Kip1) signaling: Transcriptional and post-translational regulation.
Dong et al., Sydney, Australia. In Int J Biochem Cell Biol, Nov 2015
Phosphorylation of p27(Kip1) at Thr(187) and Ser(10) is a prerequisite for its degradation via the E3 ubiquitin ligases SKP2 (nuclear) and KPC (cytoplasmic), respectively.
Involvement of F-BOX proteins in progression and development of human malignancies.
Mohammad et al., Doha, Qatar. In Semin Cancer Biol, Oct 2015
This review will highlight the recent literature on three well characterized FBPs SKP2, Fbw7, and beta-TRCP.
The role of Skp2 and its substrate CDKN1B (p27) in colorectal cancer.
Berindan-Neagoe et al., Cluj-Napoca / Kolozsvár, Romania. In J Gastrointestin Liver Dis, Jun 2015
It has recently been shown that the S-phase kinase-associated protein 2 (Skp2) overexpression plays an important role in the pathogenesis of colorectal cancer.
The role of the ubiquitin proteasome system in cerebellar development and medulloblastoma.
Marzban et al., Winnipeg, Canada. In Mol Brain, 2014
We propose the hypothesis that proteasomal activity is essential to regulate the critical transition between proliferating granule cells and differentiated granule cells and that proteasome dysfunction may lead to MB. Proteasome dysfunction could also account for various mutations in MBs resulting from deficiencies in DNA checkpoint and repair mechanisms prior to development of MBs.Data showing a role for the ubiquitin ligases β-TrCP, FBW7, Huwe1, and SKP2 in MBs suggest the possibility of a classification of MBs based on the expression (over expression or under expression) of specific ubiquitin ligases which function as oncogenes, tumor suppressors or cell cycle regulators.
Rb suppresses human cone-precursor-derived retinoblastoma tumours.
Cobrinik et al., New York City, United States. In Nature, 2014
Proliferation of Rb-depleted cones and retinoblastoma cells also depended on the Rb-related protein p107, SKP2, and a p27 downregulation associated with cone precursor maturation.
Acetylation-dependent regulation of Skp2 function.
Wei et al., Boston, United States. In Cell, 2012
Studies provide a mechanism whereby acetylation of Skp2 by p300 regulates protein stability and cellular localization, thus modulating oncogenic signaling.
Inhibition of S-phase kinase-associated protein 2 (Skp2) reprograms and converts diabetogenic T cells to Foxp3+ regulatory T cells.
Liu et al., Duarte, United States. In Proc Natl Acad Sci U S A, 2012
findings support the critical role of Skp2 in functional specification of Tpaths and Tregs, and demonstrate an important molecular mechanism mediating Skp2 function in balancing immune tolerance during autoimmune disease development.
The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis.
Lin et al., Houston, United States. In Cell, 2012
The Skp2 SCF complex, not TRAF6, is a critical E3 ligase for ErbB-receptor-mediated Akt ubiquitination and membrane recruitment in response to EGF.
Skp2 expression unfavorably impacts survival in resectable esophageal squamous cell carcinoma.
Yang et al., Guangzhou, China. In J Transl Med, 2011
Negative Skp2 expression in primary resected esophageal squamous cell carcinoma is an independent factor for better survival.
The amelioration of renal damage in Skp2-deficient mice canceled by p27 Kip1 deficiency in Skp2-/- p27-/- mice.
Kitagawa et al., Hamamatsu, Japan. In Plos One, 2011
a pathogenic role of the reduction in p27 targeted by Skp2 in the progression of nephropathy in unilateral ureteral obstruction
Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer.
Pagano et al., New York City, United States. In Nat Rev Cancer, 2008
Here, we explore the functionality and biology of the F-box proteins, SKP2 (S-phase kinase-associated protein 2) and beta-TrCP (beta-transducin repeat-containing protein), which are emerging as important players in cancer biogenesis owing to the deregulated proteolysis of their substrates.
Deathproof: new insights on the role of skp2 in tumorigenesis.
Reed, Los Angeles, United States. In Cancer Cell, 2008
The F box protein Skp2 is frequently overexpressed in human tumors and is capable of transforming cultured cells in vitro.
Regulation of p27 by S-phase kinase-associated protein 2 is associated with aggressiveness in non-small-cell lung cancer.
Maehara et al., Fukuoka, Japan. In J Clin Oncol, 2004
Skp2 overexpression is closely associated with the suppression of p27 and the aggressiveness in NSCLC.
Bioluminescent imaging of Cdk2 inhibition in vivo.
Kaelin et al., Boston, United States. In Nat Med, 2004
The cyclin-dependent kinase (Cdk) inhibitor p27, for example, is polyubiquitylated in a cell cycle-dependent manner by a ubiquitin ligase complex containing the F-box protein Skp2.
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