The degradation of p27 via Skp2 requires the accessory protein CKS1B. (wikipedia.org)
To prevent premature degradation of p27, Skp2 levels are kept low during early and mid-G1 due to the APC/CCdh1ubiquitin ligase, which mediates the ubiquitylation of Skp2. (wikipedia.org)
Skp2 is the substrate recruiting component of the SCFSkp2 complex, which targets cell cycle control elements, such as p27 and p21. (wikipedia.org)
Here, SKP2 has been implicated in double negative feedback loops with both p21 and p27, that control cell cycle entry and G1/S transition. (wikipedia.org)
SKP2 overexpression is associated with increased serine 10 phosphorylation of p27 (pSer10p27) in triple-negative breast cancer. (umass.edu)
S-phase kinase-associated protein 2 (SKP2) is an important cell cycle regulator, targeting the cyclin-dependent kinase (CDK) inhibitor p27 for degradation, and is frequently overexpressed in breast cancer. (umass.edu)
Immunohistochemistry (IHC) of SKP2, p27, pSer10p27, and other genes involved in this pathway, was analyzed in 188 breast tumors and 50 benign reduction mammoplasty samples. (umass.edu)
Schepers H, Wierenga AT, Eggen BJ, Vellenga E. Oncogenic Ras blocks transforming growth factor-beta-induced cell-cycle arrest by degradation of p27 through a MEK/Erk/SKP2-dependent pathway. (rug.nl)
Biochemical and genetic experiments have demonstrated that Skp2 is required for the ubiquitination and consequent degradation of p27 in cultured mammalian cells and in vitro reconstitution assays. (thermofisher.com)
PD-1 suppressed the transcription of SKP2 , the substrate recognition component of the SCF Skp2 ubiquitin ligase that leads p27 kip1 to degradation and resulted in accumulation of p27 kip1 (Figure 2). (shu.edu)
MATERIALS AND METHODS: The expression of Skp2, Cks1, and p27 Kip1 was examined by immunohistochemistry using highly specific antibodies on formalin-fixed, paraffin-embedded tissue sections from 80 patients with colorectal carcinoma. (haifa.ac.il)
RESULTS: Overexpression of Skp2 and Cks1 strongly correlated with loss of p27 Kip1 and loss of tumor differentiation. (haifa.ac.il)
increase SKP2 expression through TEAD\YAP activity, which subsequently assembles the Skp2/Skp1\Cullin\F\box (SCFS kp2) complex resulting in degradation from the cell routine inhibitors p21/p27. (rawveronica.com)
If YAP is normally inactivated, for instance, when cells develop on gentle substrates, SKP2?amounts are low, p21/p27 protein accumulate resulting in cell routine exit. (rawveronica.com)
From some tests, where endogenous INNO-406 inhibitor database YAP was depleted with or with no SKP2 goals p21 and p27 jointly, Jang (2017) figured SKP2 could be, at least in a few cells, the main element regulator of YAP depletion\induced cell routine leave at G0. (rawveronica.com)
Initial, overexpression of SKP2 was enough to counteract cell senescence induced by p21/p27 stabilization upon YAP depletion. (rawveronica.com)
Previous studies established that EBNA3C facilitates degradation of several vital cell cycle regulators, including the retinoblastoma (pRb) and p27(KIP) proteins, by recruitment of the SCF(Skp2) E3 ubiquitin ligase complex. (interleukinreceptor.com)
In the present study, we examined the clinical and biological significance of Skp2 expression in human gastric carcinoma and the relationship between the expression of Skp2 and p27. (elsevierpure.com)
Western blot analysis showed that Skp2-transfected cells expressed lower levels of p27 protein than the control cells. (elsevierpure.com)
These findings indicate that Skp2 expression can modulate the malignant phenotype of gastric carcinoma, possibly via p27 proteolysis. (elsevierpure.com)
KIP110
It specifically recognizes and promotes the degradation of phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also referred to as p27 or KIP1) predominantly in S, G2 phase, and the initial part of the M phase. (wikipedia.org)
Phospho-p27 Kip1 (Thr198) Antibody detects endogenous levels of p27 Kip1 only when phosphorylated at Threonine 198. (affbiotech.cn)
What are the effects of p27 kip1 and p15 INK4 ? (shu.edu)
Cell cycle progression is faster in cells in which invadopodia are abolished (by Tks5 knockdown), evidenced by earlier induction of cyclins A and B. A close look at the regulators of G1 revealed that the overexpression of p27 kip1 , but not p21 cip1 , causes faster turnover of invadopodia and increased ECM degradation. (biorxiv.org)
Furthermore, both endogenous and over-expressed p27 kip1 localizes to the sites of invadopodia assembly. (biorxiv.org)
In recent years, cell cycle regulators have been shown to exhibit roles in both tumor suppression and tumor promotion, particularly cyclin-dependent kinase inhibitors (CKI) p27 kip1 and p21 cip1 14 . (biorxiv.org)
BACKGROUND: Loss of the cell-cycle inhibitory protein p27 Kip1 is associated with poor prognosis in colorectal carcinoma. (haifa.ac.il)
The decrease in p27 Kip1 levels is the result of increased proteasome-dependent degradation, mediated and rate-limited by its specific ubiquitin ligase subunits S-phase kinase protein (Skp) 2 and cyclin-dependent kinase subunit (Cks) 1. (haifa.ac.il)
Each protein provided significant additional prognostic information to that given by disease stage, tumor grade, or p27 Kip1 expression. (haifa.ac.il)
The cyclin-dependent kinase (CDK) inhibitor p27(Kip1) is a key cell-cycle regulator of G1-to-S phase transition [ 1 ]. (biomedcentral.com)
Inhibitor p273
The cyclin dependent kinase inhibitor p27 is one of the most frequently dysregulated tumour suppressor protein in human cancers. (nottingham.ac.uk)
Evidence is presented that calpain, a calcium-activated protease, degrades the cyclin-dependent kinase inhibitor, p27, during the mitotic clonal expansion phase of 3T3-L1 preadipocyte differentiation. (bvsalud.org)
Among the diverse signaling outcomes associated with ubiquitination, the most well-established is the targeted degradation of substrates via the proteasome. (intechopen.com)
CUL4A acts as a scaffold proteins to create a CUL4A-DDB1-Band complicated and regulates many mobile pathways by concentrating on a number of protein for ubiquitination and degradation. (healthandwellnesssource.org)
The ubiquitin proteasome system (UPS) regulates the expression levels of cellular proteins by ubiquitination of protein substrates followed by their degradation via the proteasome. (biomedcentral.com)
Overexpression2
Inhibition of calpain by either ALLN or by overexpression of calpastatin blocks the degradation of p27. (bvsalud.org)
Mechanistically, overexpression of BCRC-3 induced the expression of cyclin-dependent kinase inhibitor 1B (p27). (biomedcentral.com)
Proteins7
the ubiquitin-proteasome system mediates the degradation of these mitotic regulatory proteins, controlling their intracellular concentrations. (wikipedia.org)
It may represent an accumulation of misfolded, damaged or unwanted proteins, awaiting or undergoing degradation. (biomedcentral.com)
This observation suggests the existence of one or more proteins induced or activated by IFNα that directly or indirectly protect SAMHD1 from degradation. (biomedcentral.com)
These proteins were rescued by the proteasome inhibitor MG132, indicating the autocatalytic degradation of F-box proteins upon loss of CSN2 or CSN5. (biomedcentral.com)
The regulated expression and degradation of proteins are critical to all aspects of cell development and proliferation. (biomedcentral.com)
A key component involved in regulating degradation of proteins by the UPS is the COP9 signalosome (CSN). (biomedcentral.com)
On the one hand, the UPS acts as a host defense mechanism to selectively recognize HBV proteins as well as special cellular proteins that favor the viral life cycle and induces their ubiquitin-dependent proteasomal degradation to limit HBV infection. (biomedcentral.com)
Proteasome3
Like the endogenous HPK1, both wild-type HPK1 and its kinase-dead mutant, HPK1-M46, overexpressed in Panc-1 cells, were also targeted by proteasome-mediated degradation. (aacrjournals.org)
A reduction in the level of cellular p27 is frequently due to increased proteasome-dependent degradation. (nottingham.ac.uk)
Recently, studies show that the macrocyclic octapeptide argyrin A induced an increase in cellular p27 levels by preventing the turnover of the protein via inhibition of proteasome function. (nottingham.ac.uk)
Ubiquitin2
In particular, ubiquitin-mediated degradation is critically important at transition points where it provides directionality and irreversibility to the cell cycle, which is essential for maintaining genome integrity. (intechopen.com)
The COP9/signalosome (CSN) is a highly conserved eight subunit complex that, by deneddylating cullins in cullin-based E3 ubiquitinligases, regulates protein degradation. (biomedcentral.com)
Regulates4
p27 regulates G1 /S transition by abrogating the activity of cyclin/CDK complexes. (umass.edu)
Cul4a targets p27 for degradation and regulates proliferation, cell cycle exit, and differentiation during erythropoiesis. (biomedcentral.com)
P27 is a cyclin-dependent kinase inhibitor that negatively regulates cell proliferation. (springeropen.com)
12. Li B, Jia N, Kapur R, Chun KT: Cul4A targets p27 for degradation and regulates proliferation, cell cycle exit, and differentiation throughout erythropoiesis. (gpr44.com)
MRNA degradation2
They can bind to the 3untranslated region (3UTR) of target genes, resulting in the target mRNA degradation or translational repression [8, 9]. (researchdataservice.com)
Shortening of poly(A) tail to 30 to 60 nucleotides in mammalian cellular material is necessary for mRNA degradation (30). (careersfromscience.org)
Inhibitors1
As an alternative approach to such conventional inhibitors, the first-in-class small molecule sEH degraders were recently developed by our group that promote the degradation of sEH within cells with superior cellular efficacy compared to sEH inhibitors. (einsteinmed.edu)
Cellular3
In breast cancer, the cellular structures responsible for ECM degradation are invadopodia. (biorxiv.org)
Nevertheless, it's been argued that the principal degradation pathway in mammalian cellular material is certainly mediated by exosomes, complexes made up of at least ten 3-5 exonucleases (28, 31, 32). (careersfromscience.org)
As a highly conserved cellular degradation mechanism, the UPS affects a variety of biological processes and participates in viral propagation. (biomedcentral.com)
Mitotic3
p27 is degraded in vitro by cell-free extracts from clonally expanding preadipocytes that contain "active" calpain but not by extracts from pre-mitotic preadipocytes that do not. (bvsalud.org)
Thus, extracellular signals from the differentiation inducers appear to activate calpain, which degrades p27 allowing density-dependent inhibited preadipocytes to reenter the cell cycle and undergo mitotic clonal expansion. (bvsalud.org)
We additional display that CUL4A-mediated RASSF1A degradation takes place during depletion and mitosis of CUL4A markedly reverses mitotic-phase-stimulated RASSF1A degradation. (healthandwellnesssource.org)
Pathway1
Amino acid deficiencies also up-regulate the expression of p27 using some components of this pathway. (biomedcentral.com)
Tumor2
In the present study, we investigated the significance of survivin and P27 expressions in UC of the urinary bladder, by correlating their expression with clinicopathological features, including tumor pattern (papillary or solid), grade of differentiation, and stage of invasion (non-muscle or muscle-invasive). (springeropen.com)
BCRC-3 functions as a tumor inhibitor to suppress BC cell proliferation through miR-182-5p/p27 axis, which would be a novel target for BC therapy. (biomedcentral.com)
Protein expression3
Preliminary studies using either N -methyl- N -nitrosourea (MNU)-induced rat breast cancer model or human breast cancer cell lines in vitro had suggested, but not proved, that nutritional and chemopreventive anti-cancer agents increase p27 protein expression. (biomedcentral.com)
This apparent increase in p27 protein expression might have been due to either increased synthesis or decreased degradation, or a combination of both [ 1 ]. (biomedcentral.com)
This study provided evidence that the up-regulation of p27 protein expression is at least in part due to increased synthesis and that this increase fairly faithfully recapitulates the cancer preventive activity of nutritional and chemopreventive anti-cancer agents. (biomedcentral.com)
P27 is inactivated in cancer cells by various mechanisms including impaired synthesis, accelerated degradation, and mislocalization. (springeropen.com)
Kinase4
p27 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclin E-CDK2, which phosphorylates pRb, thereby ushering the cell from G1 into S phase through the Restriction point (Figure 2). (shu.edu)
P27 is a cyclin-dependent kinase inhibitor (CKI) that controls protein synthesis during the cell cycle. (springeropen.com)
b) 4-Hydroxytamoxifen (but not tamoxifen), genistein (but not genistin), daidzein, and probably other nutritional and chemopreventive anti-cancer agents could up-regulate expression of p27 via receptor protein tyrosine kinases (RPTKs), phosphoinositide 3-kinase (PI3K), phosphoinosite-dependent kinase (PDK), Akt/PKB and mTOR. (biomedcentral.com)
Reduced expression level of p27, a cyclin-dependent kinase inhibitor, is associated with high aggressiveness and poor prognosis of various malignant tumors, including gastric carcinoma. (elsevierpure.com)
Vitro1
Preliminary studies using in vivo model of MNU-induced rat mammary cancer and in vitro model of cultured cells had suggested - but not proved - that various nutritional and chemopreventive anti-cancer agents, including moderate dietary restriction, up-regulated the expression of p27 (Fig. 1a ). (biomedcentral.com)
Complexes1
Transcriptional and translational control, sequestration in cyclin D1 complexes and localization all regulate p27 in G1 phase. (biomedcentral.com)
Nucleus1
Accumulation of p27 in the nucleus, therefore, blocks cell cycle progression of T-lymphocytes that are being induced to act against cancer antigens. (shu.edu)
Synthesis1
Further studies were conducted to gain some insight into the molecular basis of this increase in the synthesis of p27. (biomedcentral.com)
Cells6
Both survivin and P27 were absent in urothelial cells of mild chronic cystitis lesions while expressed in 60% and 43.3% of UCs, respectively. (springeropen.com)
22 ] showed that interferon alpha (IFNα) treatment of THP1 cells prevents degradation of SAMHD1 following incubation with SIV MAC virus-like particles containing Vpx (VLPs-Vpx). (biomedcentral.com)
This report addresses the question of whether various nutritional and chemopreventive anti-cancer agents up-regulate the expression of p27 in preneoplastic and neoplastic cells. (biomedcentral.com)
Experimental evidence presented in the first half of this report shows that these agents fairly faithfully up-regulate expression of p27 in mouse epidermal (JB6) and human breast cancer (MCF7, MDA-MB-321, and AU565) cells. (biomedcentral.com)
Based on these findings, we conclude that various nutritional and chemopreventive anti-cancer agents up-regulate expression of p27 in (pre)neoplastic cells. (biomedcentral.com)
2006. Accelerated degradation of FADD and procaspase 8 in cells expressing human papilloma virus 16 E6 impairs TRAIL-mediated apoptosis. (virosin.org)
Certainly, mRNAs of some regulatory substances, such as for example c-myc, cyclins, p27, cyclooxygenase-2 (Cox-2), and interleukin 2 (IL-2), are short-lived normally, and their balance is certainly subject to alter upon external arousal (29). (careersfromscience.org)
Associated with poor1
High score of survivin and low score of P27 were associated with poor prognostic factors of UC (solid pattern, high grade, and deep tumors). (springeropen.com)
Promote1
Importantly, BCRC-3 could directly interact with miR-182-5p, and subsequently act as a miRNA sponge to promote the miR-182-5p-targeted 3'UTR activity of p27. (biomedcentral.com)
Activity1
To address this question, the effects of various nutritional and chemopreventive anti-cancer agents on the activity of the proximal 5'-upstream region of p27 gene were investigated by transient transfection assay. (biomedcentral.com)
Manner1
This response is triggered in a p19Arf/p53-independent, but p27-dependent manner. (wikipedia.org)