• This protein is reported to be involved in the degradation of cyclin-dependent kinase inhibitor CDKN1B/p27Kip1. (wikipedia.org)
  • S-phase kinase-associated protein 2 (Skp2), a member of the F-box family of substrate-recognition subunits of Skp1-Cullin-F-box ubiquitin-protein ligase complexes, is necessary for p27 ubiquitination and degradation. (elsevierpure.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)
  • 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 ubiquitin ligases, regulates protein 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)
  • crucial the different parts of PN will be the molecular chaperones and both primary degradation machineries, specifically the autophagy/lysosome pathway (ALP) as well as the ubiquitin/proteasome program (UPS) (28, 52). (lavoixdesrroms.org)
  • The process of the degradation of the hypoxia-inducible factors (HIFs) that mainly regulate oxygen and iron dependent activity of enzymes require DHL tumor suppressor. (standardofcare.com)
  • The main action of the VHL protein is ubiquitin ligase activity resulting in protein degradation. (standardofcare.com)
  • Here we report that Tel2 and Tti1 are targeted for degradation within mTORC1 by the SCFFbxo9 ubiquitin ligase to adjust mTOR signalling to growth factor availability. (cipsm.de)
  • The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. (cancerindex.org)
  • Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. (thermofisher.com)
  • This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. (cancerindex.org)
  • Greater than 95% knockdown of the non-catalytic subunit CSN2 and the deneddylating subunit CSN5 of the CSN was achieved in the human myeloid progenitor cell line K562. (biomedcentral.com)
  • protein phosphatase 1 catalytic subunit a. (gsea-msigdb.org)
  • The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. (cancerindex.org)
  • A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. (lookformedical.com)
  • An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. (lookformedical.com)
  • Mammalian aurora-A belongs to a multigenic family of mitotic serine/threonine kinases comprising two other members: aurora-B and aurora-C. In this review we will focus on aurora-A that starts to localize to centrosomes only in S phase as soon as centrioles have been duplicated, the protein is then degraded in early G1. (lookformedical.com)
  • A family of serine/threonine kinase Aurora constitutes a key regulator in the orchestration of mitotic events. (lookformedical.com)
  • Five members of the Plk family have been discovered in humans and these serine/threonine kinases have emerged as key players by performing crucial functions in the cell cycle, DNA damage response and neuron biology [ 2 - 6 ]. (oncotarget.com)
  • E6-AP) is an important member of the ubiquitin proteasome system and a type of ubiquitin protein ligase (E3 enzyme) ( 6 ). (spandidos-publications.com)
  • Ubiquitin Proteasome System Current Insights into Mechanism Cellular Regu. (intechopen.com)
  • Specifically, the boundary between G1 and S-phase is tightly regulated by the ubiquitin proteasome system. (intechopen.com)
  • Numerous E3 ubiquitin ligases, which facilitate the ubiquitination of specific substrates, have been shown to control G1/S. In this chapter, we will discuss components in the ubiquitin proteasome system that are implicated in G1/S control, how these enzymes are interconnected, gaps in our current knowledge, and the potential role of these pathways in the cancer cycle and disease proliferation. (intechopen.com)
  • The two main routes for eukaryotic intracellular protein clearance are the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway. (biomedcentral.com)
  • The COP9 signalosome: an assembly and maintenance platform for cullin ubiquitin ligases? (wikipedia.org)
  • The largest known class of E3 ubiquitin ligases comprises the Cullin-RING ligases (CRLs) of which the best studied is the SCF (Skp1, Cul1, F-box protein) complex [ 16 ]. (biomedcentral.com)
  • Since each cullin (Cul1-5) forms complexes with a variable substrate recognition subunit (SRS) (F-box proteins for Cul1 as above, VHL box proteins for Cul2, BTB proteins for Cul3, WD40 proteins for Cul4 and SOCS box proteins for Cul5, reviewed in [ 20 ]) specificity in CRL target protein recruitment is achieved by the large number of variable SRS containing CRLs. (biomedcentral.com)
  • In this work, we identified oroxylin A (OA), a dual GLUT1/mitochondrial fusion inhibitor, which restricted glucose catabolism of hepatocellular carcinoma cells and simultaneously inhibited mitochondrial fusion by disturbing SIRT1/PDK2/PARL axis. (bvsalud.org)
  • Collectively, these finding indicate that combining a GLUT1 inhibitor with a mitochondrial fusion inhibitor can work synergistically in cancer therapy and, more broadly, suggest that the incorporations of mitochondrial dynamics and metabolic regulation may become the targetable vulnerabilities bypassing the genotypic heterogeneity of multiple malignancies. (bvsalud.org)
  • The E3 ligase interacts with the protein substrate and thus confers the specificity of the UPS [ 16 ]. (biomedcentral.com)
  • Aurora kinase C is a chromosomal passenger protein that interacts with aurora kinase B in the regulation of MITOSIS. (lookformedical.com)
  • HIF2A interacts with cyclin D1, leading to increased survival due to lower rates of apoptosis and increased proliferation due to the activation of cyclin D1. (standardofcare.com)
  • COP9 constitutive photomorphogenic homolog subunit 5 (Arabidopsis), also known as COPS5 or Csn5, is a gene conserved from humans to Saccharomyces cerevisiae. (wikipedia.org)
  • The protein encoded by this gene is one of the eight subunits of COP9 signalosome, a highly conserved protein complex that functions as an important regulator in multiple signaling pathways. (wikipedia.org)
  • The zinc finger domain of Tzfp binds to the tbs motif located at the upstream flanking region of the Aie1 (aurora-C) kinase gene. (lookformedical.com)
  • This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). (thermofisher.com)
  • Although the senescent cells remain viable, they show typical changes with enlarged and flattened cell bodies, apoptosis resistance, increased activity of senescence-associated β -galactosidase (SA- β -gal), and upregulation of cyclin-dependent kinase (CDK) inhibitors including p16 INK4A , ARF proteins, and p21 [ 13 - 16 ]. (hindawi.com)
  • In addition, numerous important cellular proteins, such as B-cell lymphoma-2 homologous antagonist/killer, Myc proto-oncogene protein, cyclin-dependent kinase inhibitor 1B, DNA replication licensing factor MCM-7, retinoblastoma 1 and Annexin A1, are degenerated through the UBE3A-mediated ubiquitin proteasome pathway ( 7 ). (spandidos-publications.com)
  • The activity of CDKs is controlled by their binding to coactivator subunits termed Cyclins, as well as by CDK inhibitory proteins termed CKIs. (intechopen.com)
  • The accumulation of both Cyclin and CKI proteins is tightly regulated at the level of transcription. (intechopen.com)
  • In addition, Cyclin and CKI proteins are controlled at the level of their destruction. (intechopen.com)
  • 6. Activation of endogenous Sgg/Gsk-3 in genes (A1), and consultant blots teaching 20S- proteasome subunit manifestation and total proteins ubiquitination (A2) in little fly cells after inducible RNAi-mediated Pdpk1 knockdown for 6 times. (lavoixdesrroms.org)
  • ubiquitin conjugating enzyme E2 D3 [Sourc. (gsea-msigdb.org)
  • The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. (lookformedical.com)
  • These events resulted in upregulation of the Cdk4/6 inhibitor p15 INK4B and repression of the Cdk-activating phosphatase Cdc25A. (shu.edu)
  • P15 INK4 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclind-CDK4,6, inhibiting it from hypophosphorylating Rb, thereby, rendering the cell cycle unresponsive to external proliferation signals. (shu.edu)
  • Full holoenzyme activity of the cyclin D1-Cdk4 complex is induced by mitogen recruitment of CAK. (shu.edu)
  • The cyclin D1-Cdk4 complex phosphorylates the pRB protein leading to sequential phosphorylation by cyclin E-Cdk2 and release of free E2F. (shu.edu)
  • This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. (cancerindex.org)
  • CDK4 is a member of the Ser/Thr protein kinase family. (thermofisher.com)
  • cyclin dependent kinase 5 regulatory s. (gsea-msigdb.org)
  • The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). (thermofisher.com)
  • Progression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). (intechopen.com)
  • Many indirubins by performing through competition with ATP binding are actually dual inhibitors of both cyclin-dependent kinases (CDKs) and glycogen synthase kinase-3 (Gsk-3and -inhibitor (38), while research in tumor cells suggested it. (lavoixdesrroms.org)
  • They further link to the activation of protein kinase C- (PKC-) induced generation of reactive oxygen species (ROS) [ 6 , 7 ], which further mediates the activation of downstream transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF- κ B). Thus, the main treatments of DN refer to modulate glycemic and blood pressure through insulin and RAS inhibitors. (hindawi.com)
  • Canonical Notch signaling activates the transcription of BMI1 proto‑oncogene polycomb ring finger, cyclin D1, CD44, cyclin dependent kinase inhibitor 1A, hes family bHLH transcription factor 1, hes related family bHLH transcription factor with YRPW motif 1, MYC, NOTCH3, RE1 silencing transcription factor and transcription factor 7 in a cellular context‑dependent manner, while non‑canonical Notch signaling activates NF‑κB and Rac family small GTPase 1. (spandidos-publications.com)
  • High throughput in vitro seed germination screen identified new ABA responsive RING-type ubiquitin E3 ligases in Arabidopsis thaliana. (helsinki.fi)
  • Genomic and phenomic screens for flower related RING type ubiquitin E3 ligases in Arabidopsis. (helsinki.fi)
  • Overexpression of the Arabidopsis Anaphase Promoting Complex subunit CDC27a increases growth rate and organ size. (helsinki.fi)
  • The Pol II activator cyclin-dependent kinase 9 (CDK9) was similarly enriched across IGSs (Extended Data Fig. 1g ). (nature.com)
  • Structure of cDNAs encoding human eukaryotic initiation factor 3 subunits. (wikipedia.org)
  • Mature rRNAs are packaged into 40S and 60S ribosomal subunits for export to the cytoplasm. (nature.com)
  • An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. (lookformedical.com)
  • In addition, compared to the mono-treatment, combination of Polo-like kinase 1 inhibition with anti-mitotic or DNA damaging agents boosts more severe mitotic defects, effectually triggers apoptosis and strongly inhibits proliferation of cancer cells with functional p53. (oncotarget.com)
  • SCF Pop1p-Pop2p mediated Rum1p ubiquitylation in vitro ( 2A ) Various Cdc2p complexes were affinity purified from cells co-expressing 6 × His-Myc-tagged Cdc2p and HA-tagged cyclins on nickel NTA resin. (biomedcentral.com)
  • Bacterially expressed, phosphorylated Rum1p, derived from the preparation shown in Fig. 2A was incubated with Pip1p complexes immunopurified from the indicated strains, human E1, UBC3 (hUBC3), ATP, and ubiquitin for 90 min at 30°C. Reactions were stopped by the addition of SDS sample buffer, and reaction products were separated by SDS PAGE and visualized by autoradiography. (biomedcentral.com)
  • Moreover, PD-1 and PD-L1 inhibitors are being tested in combination with other checkpoint inhibitors, targeted therapies, cancer vaccines, monoclonal antibodies, and other modalities. (shu.edu)
  • Small-molecule inhibitors, antagonistic monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), bispecific antibodies or biologics (bsAbs) and chimeric antigen receptor-modified T cells (CAR-Ts) targeting Notch signaling components have been developed as investigational anti-cancer drugs ( 10 - 12 ). (spandidos-publications.com)
  • UBE3A is associated with cervical cancer and may combine with the E6 proto-oncogene encoded by HPV16 within cervical cancer cells to form the E6/E6-AP protein complex through the ubiquitin proteasome pathway ( 4 ). (spandidos-publications.com)
  • An aurora kinase that is a component of the chromosomal passenger protein complex and is involved in the regulation of MITOSIS. (lookformedical.com)
  • Recognition of the 30-splice site is a key step in premRNA splicing and accomplished by a dynamic complex comprising splicing factor 1 (SF1) and the U2 snRNP auxiliary factor 65-kDa subunit (U2AF65). (cipsm.de)
  • Recently, clinical trials of immune checkpoint inhibitor plus vascular endothelial growth factor receptor-tyrosine kinase inhibitor (TKI) for mRCC have exhibited outstanding efficacies [ 3 - 5 ]. (e-crt.org)
  • In contrast, MM patients who received immune checkpoint inhibitors (ICIs) had a significantly more favorable OS (HR 0.39, 95% CI 0.20-0.75, P = 0.008). (bvsalud.org)
  • We demonstrate that transient receptor potential vanilloid 4 (TRPV4) is a promoting regulator of sc polarity via activating Ca2+-dependent AMPK/MLC/ERM pathway. (bvsalud.org)
  • Equipped with a mouse model of stress (5-HT1A-R-/- mice) and a 5-HT1A-R-expressing hippocampal neuron-derived cell line, HN2-5, our earlier studies have reported that a 5-HT1A-R-mediated signaling pathway functions via extracellular receptor-activated kinase 1/2 (ERK1/2)-catalyzed activation of protein kinase C alpha (PKC) to promote synaptogenesis at P15 in the hippocampal CA1 region [12,16]. (thetechnoant.info)
  • The overexpression of miRNA‑375 significantly suppressed the levels of protein expression of ubiquitin‑protein ligase E3A (UBE3A) and Insulin‑like growth factor‑1 receptor (IGF‑1R) in HPV‑18(+) cervical cancer cells. (spandidos-publications.com)
  • Plk1 inhibitors target all rapidly dividing cells irrespective of tumor cells or non-transformed normal but proliferating cells. (oncotarget.com)
  • In this regard, restoration of p53 in tumor cells with loss or mutation of p53 will reinforce the cytotoxicity of combined Polo-like kinase 1 therapy and provide a proficient strategy for combating relapse and metastasis of cancer. (oncotarget.com)
  • COP9 constitutive photomorphogenic homolog subunit 5 has been shown to interact with Macrophage migration inhibitory factor, GFER, BCL3, Ubiquitin carboxy-terminal hydrolase L1, S100A7 and C-jun. (wikipedia.org)
  • Both, Cdc2p/Cdc13p and Cdc2p/Cig1p produced a shift in Rum1p migration indicative of phosphorylation, although it is unclear whether both kinases target the same residues [ 21 ]. (biomedcentral.com)
  • Those transformed cells form tumours when implanted in immunodeficient mice, indicating that the kinase is an oncogene. (lookformedical.com)
  • We conclude that CSN2 is required for CSN integrity and the stability of individual CSN subunits, and postulate that CSN2 loss results in a phenotype distinct from that of cells lacking CSN5 possibly as a consequence of altered CSN5 activity within a resultant CSN subcomplex. (biomedcentral.com)
  • The overexpression of miRNA‑375 significantly increased caspase‑3 and caspase‑9 activities, induced B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein, tumor protein 53 and cyclin‑dependent kinase inhibitor 1 protein expression and suppressed cyclin D1 and survivin protein expression in HPV‑18(+) cervical cancer cells. (spandidos-publications.com)
  • Ectopic kinase overexpression in any culture cell line leads to polyploidy and centrosome amplification. (lookformedical.com)
  • Treatment with the deubiquitinase inhibitor of USP9X, WP1130 (Degrasyn, a small molecule compound that USP9X deubiquitinase inhibitor), also led to the accumulation of breast cancer cells in the G0/G1 phase, but this effect could be rescued by overexpression of CDC123. (bvsalud.org)
  • Aurora kinase c. (lookformedical.com)
  • Aurora kinases are found in all organisms in which their function has been conserved throughout evolution, namely the control of chromosome segregation. (lookformedical.com)
  • abstract = "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)
  • Polo-like kinase 1, a pivotal regulator of mitosis and cytokinesis, is highly expressed in a broad spectrum of tumors and its expression correlates often with poor prognosis, suggesting its potential as a therapeutic target. (oncotarget.com)
  • p53 represses the promoter of Polo-like kinase 1, whereas Polo-like kinase 1 inhibits p53 and its family members p63 and p73 in cancer cells lacking functional p53. (oncotarget.com)
  • Since the discovery of Polo kinase in Drosophila in 1988 [ 1 ], the Polo-like kinase (Plk) family has been attracting enormous attention, both in academia and in pharmaceutical industry. (oncotarget.com)
  • Notably, we discovered that Brg1, however, not its family Arid1a and BRM, was elevated in depleted DLD1 and HCT116 cells (Fig.?1a and Supplementary Figure?1a), in which, c-Myc and Cyclin E, two well-characterized canonical FBW7 substrates, BSF 208075 manufacturer were used as positive controls25,26. (buyresearchchemicalss.net)
  • Receptor-regulated SMADs (R-SMADs), SMAD1, 2, 3, 5, and 8, are the only SMADs directly phosphorylated and activated by the kinase domain of type I receptors. (shu.edu)
  • The Notch signaling network exerts oncogenic and tumor‑suppressive effects in a cancer stage‑ or (sub)type‑dependent manner. (spandidos-publications.com)
  • However, the physiological role of Brg1 in tumorigenesis is rather complicated, and seems to be tissue type and cellular context dependent. (buyresearchchemicalss.net)
  • Agonist (100 nM 8-OH-DPAT) (D) treatment of freely dividing HN2-5 cells caused stimulation of PKC (Physique 1a) [25,26,27,28,29], which was blocked by the 5-HT1A-R antagonist WAY100635 (WAY) (10 M) but not by an inhibitor of the ERK1/2 kinase MEK (U0126) (U) (10 M) (Physique 1a). (thetechnoant.info)
  • Ectopic expression of PtaRHE1, encoding a poplar RING-H2 protein with E3 ligase activity, alters plant development and induces defence related response in tobacco. (helsinki.fi)
  • 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)