• However, in recent years, new evidence proved that the presence of CDK6 is not essential for proliferation in every cell type, the cell cycle has a complex circuitry of regulation and the role of CDK6 might be more important in certain cell types than in others, where CDK4 or CDK2 can act as protein kinases compensating its role. (wikipedia.org)
  • Cyclin-dependent kinases (cdks) are regulated by cyclin binding, phosphorylation and by two families of cdk inhibitors. (medscape.com)
  • Cyclins function as regulators of CDK kinases. (thermofisher.com)
  • CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. (nih.gov)
  • Cyclins and cyclin-dependent kinases (cdks) are evolutionarily conserved proteins that are essential for cell-cycle control in eukaryotes. (bdbiosciences.com)
  • The phase-dependent phosphorylation of pRB * is carried out successively by the complexes of cyclins D, E * and cyclin-dependent kinases cdk4, 6 resp. (nih.gov)
  • P61959.1 MADEKPKEGVKTENNDHINLKVAGQDGSVVQFKIKRHTPLSKLMKAYCERQGLSMRQIRFRFDGQPINETDTPAQLEMEDEDTIDVFQQQTGGVY 1367453_at NP_446195 6.42 hsp90 co-chaperone Cdc37 Cdc37 Rattus norvegicus " Co-chaperone that binds to numerous kinases and promotes their interaction with the Hsp90 complex, resulting in stabilization and promotion of their activity. (nih.gov)
  • Cell proliferation is tightly controlled by the cell-cycle regulatory proteins, primarily by cyclins and cyclin-dependent kinases (CDKs) in the G 1 phase. (molcells.org)
  • Primary drivers of the G1/S transition are the cyclin-dependent kinases (Cdks) and their activating partners, the G1 cyclins. (nih.gov)
  • In our future research we want to understand more thoroughly how cell cycle cyclin-Cdk-Cks complexes are recruited to specific promoters, how they regulate gene expression by phosphorylating RNA polymerase II and study other promoter-specific kinases capable of phosphorylating RNA-polymerase II. (nih.gov)
  • This work changed our current understanding of how the first step in the cell cycle is regulated and greatly expanded our view of the function of cell cycle-related cyclin-dependent kinases. (nih.gov)
  • Paul Nurse ABSTRACT The eukaryotic cell cycle is driven by the activity of cyclin - dependent kinases (CDKs). (biologists.com)
  • Retinoblastoma protein (Rb) interacts with cyclin-dependent kinases and regulates the transcription of genes necessary for progression through the S phase of the cell cycle. (embl-heidelberg.de)
  • Cell cycle transitions are generally triggered by variation in the activity of cyclin-dependent kinases (CDKs) bound to cyclins. (elifesciences.org)
  • Our results provide evidence that during Plasmodium male gametogony, this divergent cyclin/CDK pair fills the functional space of other eukaryotic cell-cycle kinases controlling DNA replication. (elifesciences.org)
  • Central components of these networks are the cyclin-dependent kinases (CDKs). (elifesciences.org)
  • Further studies on its effect on cyclins and cyclin-dependent kinases (CDKs) [not measured in our study] may shed light on new treatment options for COVID-19. (biomedcentral.com)
  • sample_type A C177537 GDC Value Terminology C116938 CDK4/6 Inhibition Inhibition of cyclin-dependent kinases 4 and 6 pathway activity to prevent proliferation of cancer cells and tumor growth. (nih.gov)
  • In addition to inhibition of cyclin E-cdk2, p21 and p27 also facilitate assembly and activation of cyclin D-cdks in early G1 (refs. (medscape.com)
  • p15 INK4B binds and inhibits cdk4 facilitating dissociation of p27 and cyclin D1 from cyclin D1-cdk4-p27 complexes and p27 binds and inhibits cyclin E-cdk2, leading to G1 arrest. (medscape.com)
  • In cMyc or MAPK activated cancer-derived lines, cyclin D1-cdk4/6 complexes sequester p27, and cyclin E-cdk2-inhibition is impaired. (medscape.com)
  • 5. Cdk2-dependent phosphorylation and functional inactivation of the pRB-related p130 protein in pRB(-), p16INK4A(+) tumor cells. (nih.gov)
  • 6. Regulation of E2F transcription by cyclin E-Cdk2 kinase mediated through p300/CBP co-activators. (nih.gov)
  • 9. Disruption of the actin cytoskeleton leads to inhibition of mitogen-induced cyclin E expression, Cdk2 phosphorylation, and nuclear accumulation of the retinoblastoma protein-related p107 protein. (nih.gov)
  • 13. Transduced p16INK4a peptides inhibit hypophosphorylation of the retinoblastoma protein and cell cycle progression prior to activation of Cdk2 complexes in late G1. (nih.gov)
  • 16. Phosphorylation of E2F-1 by cyclin A-cdk2. (nih.gov)
  • Unlike CDK2/cyclin A, CDK4/cyclin D3 can be inactivated by treatment with lambda-phosphatase, implying that phosphorylated T172 is accessible to a generic phosphatase while bound to a cyclin. (nih.gov)
  • The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has been implicated in the control of the G1 to S phase transition in mammals. (nih.gov)
  • CIP1 encodes a novel 21 kd protein that is found in cyclin A, cyclin D1, cyclin E, and Cdk2 immunoprecipitates. (nih.gov)
  • p21CIP1 is a potent, tight-binding inhibitor of Cdks and can inhibit the phosphorylation of Rb by cyclin A-Cdk2, cyclin E-Cdk2, cyclin D1-Cdk4, and cyclin D2-Cdk4 complexes. (nih.gov)
  • p21, also known as senescent cell-derived inhibitor 1 (Sdi1), wild-type p53-activated fragment 1 (Waf1), Cdk-interacting protein 1 (Cip1), and p53-regulated inhibitor of Cdks (Pic1) inhibits cyclin D-cdk4, cyclin E-cdk3, cyclin A-cdk2, and cyclin A-cdk1. (bdbiosciences.com)
  • Myb is substantially enhanced in S phase through modi-fication by cyclin A/cdk2, and the evidence points squarely to the major role being played by B-Myb during this phase of the cell cycle. (123dok.net)
  • In yeast, for instance, cell growth induces accumulation of Cln3 cyclin , which complexes with the cyclin dependent kinase CDK2. (wikipedia.org)
  • [3] The Cln3-CDK2 complex promotes transcription of S-phase genes by inactivating the transcriptional repressor Whi5 . (wikipedia.org)
  • During early S-phase, the cyclin E-Cdk2 complex phosphorylates NPAT , a nuclear coactivator of histone transcription. (wikipedia.org)
  • The A and B boxes each contain the cyclin-fold structural motif, with the LxCxE-binding site on the B-box cyclin fold being similar to a Cdk2-binding site of cyclin A and to a TBP-binding site of TFIIB. (embl-heidelberg.de)
  • The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)
  • These proteins, referred to as inhibitors of Cdk activity (CDkIs) bind to cyclins, cdks or their complexes. (bdbiosciences.com)
  • While it has long been known that G1 cyclin-Cdks promote the G1/S transition, surprisingly, we have little knowledge of the molecular mechanisms through which they do so. (nih.gov)
  • Malaria-causing parasites have a life cycle with unique cell-division cycles, and a repertoire of divergent CDKs and cyclins of poorly understood function and interdependency. (elifesciences.org)
  • It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. (wikipedia.org)
  • Importantly, these C-CDK complexes act as a kinase, phosphorylating and inactivating the protein of Rb and p-Rb related "pocket proteins" p107 and p130. (wikipedia.org)
  • 19. Cyclin E and c-Myc promote cell proliferation in the presence of p16INK4a and of hypophosphorylated retinoblastoma family proteins. (nih.gov)
  • The activity of these complexes is modulated by activating and inhibitory phosphorylation events, as well as by interactions with small regulatory proteins including, p16, p21, p27 and others. (bdbiosciences.com)
  • Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. (nih.gov)
  • The ternary complex containing UFD1L, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. (nih.gov)
  • Mutations in this gene as well as inits related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associatedwith tumorigenesis of a variety of cancers. (biopaqc.com)
  • The complex set of protein docking modalities cyclins use to target specific proteins for phosphorylation by their Cdk partner is only now being discovered. (nih.gov)
  • There are 61335 CYCLIN domains in 41443 proteins in SMART's nrdb database. (embl-heidelberg.de)
  • Taxonomic distribution of proteins containing CYCLIN domain. (embl-heidelberg.de)
  • The complete taxonomic breakdown of all proteins with CYCLIN domain is also avaliable . (embl-heidelberg.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing CYCLIN domain in the selected taxonomic class. (embl-heidelberg.de)
  • Structures of cyclins, Rb and TFIIB reveal that a common motif occurs in proteins regulating three consecutive events of cell-cycle control. (embl-heidelberg.de)
  • Recent results on the structures of two cyclins, cyclin A and cyclin H, and two transcription factor mediator proteins, TFIIB and the A pocket region of the retinoblastoma tumour suppressor protein (Rb), show that they share domains with a strikingly similar alpha-helical topology, despite remote sequence identity. (embl-heidelberg.de)
  • Cell survival and apoptotic regulatory proteins such as the Bcl-2 family of genes, PCNA, p16, p21, p27, and cyclin D1 are of vital importance to malignant neoplasms in prolonging cell survival. (biomedcentral.com)
  • Once the genetic material of SARS-CoV-2 enters the cell through receptor binding and then membrane fusion and penetration into the nucleus for replication, the virus controls the kinase family of enzymes and acts as switches that turn proteins on or off through the process of phosphorylation. (biomedcentral.com)
  • HN - 2006(1998) MH - Actin-Related Protein 2-3 Complex UI - D051376 MN - D5.750.78.730.246 MN - D12.776.220.525.246 MS - A complex of seven proteins including ARP2 PROTEIN and ARP3 PROTEIN that plays an essential role in maintenance and assembly of the CYTOSKELETON. (nih.gov)
  • the cyclin D. 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. (wikipedia.org)
  • The inhibitors of cdk4 (INK4) family includes p15 INK4B and the kinase inhibitor protein (KIP) family comprises p21 Kip1 and p57 Kip2 (ref. 4). (medscape.com)
  • 15. Multifaceted regulation of cell cycle progression by estrogen: regulation of Cdk inhibitors and Cdc25A independent of cyclin D1-Cdk4 function. (nih.gov)
  • D-type cyclin-CDK complexes act to inactivate the growth-suppressive function of the Rb protein through its phosphorylation, and titrate CDK inhibitors such as p21Cip1 and p27Kip1. (thermofisher.com)
  • Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)
  • CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary. (cancerindex.org)
  • SMARCA4 loss causes profound downregulation of cyclin D1, which limits CDK4/6 kinase activity in SCCOHT cells and leads to in vitro and in vivo susceptibility to CDK4/6 inhibitors. (cancerindex.org)
  • This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor Retinoblastoma protein making CDK6 an important protein in cancer development. (wikipedia.org)
  • In mammalian cells, cell cycle is activated by CDK6 in the early G1 phase through interactions with cyclins D1, D2 and D3. (wikipedia.org)
  • After the complex is formed, the C-CDK6 enzymatic complex phosphorylates the protein pRb. (wikipedia.org)
  • The CDK6 complex ensures a point of switch to commit to division responding to external signals, like mitogens and growth factors. (wikipedia.org)
  • While doing this, the CDK6 in conjunction with CDK4, act as a switch signal that first appears in G1, directing the cell towards S phase of the cell cycle. (wikipedia.org)
  • Even though CDK6 and CDK4 share 71% amino acid identity, this role in differentiation is unique to CDK6. (wikipedia.org)
  • CDK6 differs from CDK4 in other important roles. (wikipedia.org)
  • This pathway is a known route altered in cancer cells, when there is an aberrant overexpression of CDK6 and CDK4. (wikipedia.org)
  • Cyclin D1 (PRAD-1, bcl-1) is one of the key cell cycle regulators, and functions in association with cdk4 and/or cdk6 by phosphorylating the Rb protein. (thermofisher.com)
  • Cyclin D1 is a cytoplasmic and nuclear protein that is synthesized during G1 phase and assembles with either cyclin-dependent kinase 4 (CDK4) or CDK6 in response to growth factor stimulation. (thermofisher.com)
  • Cyclin D1 forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. (thermofisher.com)
  • p27 inhibits CDK6/CCND1 complex formation resulting in cell cycle arrest and inhibition of cell proliferation. (omicsdi.org)
  • In this study, Genevestigator, Kaplan-Meier Plotter, and the Human Protein Atlas databases were used to analyze the expression of p27, cell division protein kinase 6 (CDK6), and cyclin D1 (CCND1), as well as its prognostic value in different tumor tissues and corresponding normal tissues. (omicsdi.org)
  • p27 regulated the cell cycle and inhibited cell proliferation by affecting formation of the cell cycle-dependent complex CDK6/CCND1, but did not directly affect the expression of CDK6 and CCND1. (omicsdi.org)
  • NAP1L1 promotes proliferation and chemoresistance in glioma by inducing CCND1/CDK4/CDK6 expression through its interaction with HDGF and activation of c-Jun. (omicsdi.org)
  • Furthermore, HDGF could interact with c-Jun, an oncogenic transcription factor, which eventually induced the expressions of cell cycle promoters, CCND1/CDK4/CDK6. (omicsdi.org)
  • This finding suggested that NAP1L1 could interact with HDGF, and the latter recruited c-Jun, a key oncogenic transcription factor, that further induced CCND1/CDK4/CDK6 expression, thereby promoting proliferation and chemoresistance in glioma cells. (omicsdi.org)
  • Cell Cycle Protein Expression in Neuroendocrine Tumors: Association of CDK4/CDK6, CCND1, and Phosphorylated Retinoblastoma Protein With Proliferative Index. (omicsdi.org)
  • 4. Interaction of retinoblastoma protein and D cyclins during cell-growth inhibition by hexamethylenebisacetamide in TM2H mouse epithelial cells. (nih.gov)
  • Phosphorylated CDK4/cyclin D3 is active as a pRb kinase and is susceptible to inhibition by p27(Kip1). (nih.gov)
  • Further, lowered phophorylation of Rb at Ser795 by piperine treatment further suggests the inhibition of Rb hyper-phosphorylation. (bcrablinhibitor.com)
  • Finally, we found that WZ attenuated mTOR complex 1 (mTORC1) activity and upregulated mTORC2 activity, as evidenced by inhibition of the expression of the regulatory-associated protein of mTOR, phosphorylated p70 S6K, and phosphorylated ribosomal protein s6 and enhancement of the expression of Rictor in the Sertoli cells of aging mice. (bvsalud.org)
  • In BRAF V600E mutated cells inhibition of BRAF pathway lead to a decrease in ERK1/2 phosphorylation and cyclin D1 levels and an increase in p27 Kip1 . (biomedcentral.com)
  • To reveal its druggable vulnerabilities, we perform kinase-focused RNAi screens and uncover that SMARCA4-deficient SCCOHT cells are highly sensitive to the inhibition of cyclin-dependent kinase 4/6 (CDK4/6). (cancerindex.org)
  • [ 24 ] or repressing p27 expression through Akt phosphorylation of a forkhead transcription factor. (medscape.com)
  • 12. Activation of the E2F transcription factor by cyclin D1 is blocked by p16INK4, the product of the putative tumor suppressor gene MTS1. (nih.gov)
  • The CDK4-cyclinD complex normally phosphorylates the retinoblastoma protein (Rb protein), leading to release of the E2F transcription factor and cell cycle progression. (medscape.com)
  • CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. (nih.gov)
  • 26]Ohtani K,Nevins JR,Degregori J. Regulation of the Cyclin E Gene by Transcription Factor E2f1 [J].1995,92(26). (wanfangdata.com.cn)
  • Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase (PubMed:8114739, PubMed:18827403). (wuxibiortus.com)
  • One of the genes regulated through this mechanism en-codes the B-Myb transcription factor, which has been shown to be critically required for early embryonal de-velopment in the mouse. (123dok.net)
  • [3] Active cyclin D-CDK4/6 complex induces release of E2F transcription factor, which in turn initiates expression of S-phase genes. (wikipedia.org)
  • Regulatory component of the cyclin D2-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition (PubMed:8114739, PubMed:18827403). (wuxibiortus.com)
  • In budding yeast, his major finding was that the most upstream cyclin-dependent kinase complex, Cln3-Cdk1, directly phosphorylates Ser5 residues on RNA polymerase II C-terminal repeats at a specific set of promoters to activate gene expression and drive the G1/S transition. (nih.gov)
  • It phosphorylates canonical CDK motifs of components in the pre-replicative complex and is essential for DNA replication. (elifesciences.org)
  • The CERM contains a variant E2F-recognition element, and binds a complex (termed CERC) consisting of E2F4, DP1, and either p130 or p107, as well as an unidentified necessary component. (nih.gov)
  • This gene encodes one of the PPIases, which specifically binds to phosphorylated ser/thr-pro motifs to catalytically regulate the post-phosphorylation conformation of its substrates. (cancerindex.org)
  • Arp2-3 complex binds WASP PROTEIN and existing ACTIN FILAMENTS, and it nucleates the formation of new branch point filaments. (nih.gov)
  • HN - 2006 BX - Arp2-3 Complex MH - Actin-Related Protein 3 UI - D051378 MN - D5.750.78.730.246.750 MN - D12.776.220.525.246.750 MS - A component of the Arp2-3 complex that is related in sequence and structure to ACTIN and that binds ATP. (nih.gov)
  • This protein also contains an ATP-binding pocket, inhibitory and activating phosphorylation sites, a PSTAIRE-like cyclin-binding domain and an activating T-loop motif. (wikipedia.org)
  • Summary: Phosphorylation of importin-α1 by cyclin - dependent kinase 1 provides spatial and temporal control of mitotic spindle assembly through the release of spindle-assembly factors from inhibitory complexes during mitosis. (biologists.com)
  • This effect is mediated by the upregulation of a CDK inhibitor p21, which causes the decrease in cyclin D1 and CDK4 protein levels and subsequent reduction of pRb hyperphosphorylation. (molcells.org)
  • Cells exit mitosis in a specific time window without cytokinesis with a decrease in cyclin B1/cdc-2 kinase activity and MPM-2 labeling. (aacrjournals.org)
  • Thus, the p21-cyclinD1/CDK4 signaling pathway plays a critical role in ARMS/Kidins220-dependent cell-cycle progression. (molcells.org)
  • Regulates CDK7, the catalytic subunit of the CDK-activating kinase (CAK) enzymatic complex. (nih.gov)
  • The primary regulator of CDK activity is the cyclin subunit. (elifesciences.org)
  • The protein encoded by this gene is a member of the cyclin-dependent kinase, (CDK) family, which includes CDK4. (wikipedia.org)
  • In 1994, Matthew Meyerson and Ed Harlow investigated the product of a close analogous gene of CDK4. (wikipedia.org)
  • Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. (nih.gov)
  • In humans, the CCND1 gene encoding cyclin D1 is present on chromosome 11. (thermofisher.com)
  • The Cyclin D1 protein has been shown to interact with tumor suppressor protein Rb and the expression of this gene is regulated positively by Rb. (thermofisher.com)
  • C2 The Cyclin E and A genes (but not the Cyclin D gene) are strongly activated by E2F1 (DeGregori et al. (nih.gov)
  • This kinase was shown to be responsiblefor the phosphorylation of retinoblastoma gene product (Rb). (biopaqc.com)
  • Mahanine can reverse an epigenetically silenced gene, RASSF1A in prostate cancer cells by inhibiting DNMT activity that in turn down-regulates a key cell cycle regulator, cyclin D1, is an encouraging therapeutic choice for advanced prostatic cancer. (chemfaces.cn)
  • This highly unexpected finding links Cdk activity for the first time directly to transcriptional activation and contrasts with the prevailing model that RNA polymerase II phosphorylation is merely a basal step in transcriptional activation and demonstrates how direct RNA polymerase II phosphorylation at specific promoters can dynamically modulate gene expression. (nih.gov)
  • 18. The interactions of E2F with pRB and with p107 are regulated via the phosphorylation of pRB and p107 by a cyclin-dependent kinase. (nih.gov)
  • The NPLOC4-UFD1L-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. (nih.gov)
  • Scholars@Duke publication: Calcineurin regulates cyclin D1 accumulation in growth-stimulated fibroblasts. (duke.edu)
  • Although these pharmacological experiments suggested that calcineurin regulates cyclin D1 synthesis, we evaluated the effects of overexpression of activated calcineurin on cyclin D1 synthesis. (duke.edu)
  • Therefore, calcineurin is a Ca(2+)/CaM-dependent target that regulates cyclin D1 accumulation in G(1). (duke.edu)
  • Overexpression of pRb can increase the expression Cyclin D1 by an unknown mechanism (Watanabe et al. (nih.gov)
  • In SGC-7901 transfectants, ING5 overexpression caused G 1 arrest, which was positively associated with 14-3-3 overexpression, Cdk4 and c-jun hypoexpression. (oncotarget.com)
  • Cyclins (regulatory subunits) to form complexes that regulate the progression of the cell cycle. (bdbiosciences.com)
  • Many studies have reported that ARMS/Kidins220 acts as a major signaling platform in organizing the signaling complex to regulate various cellular responses in the nervous and vascular systems. (molcells.org)
  • Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (thermofisher.com)
  • Flavopiridol treatment of docetaxel-treated cells enhances the exit from mitosis with a more rapid decrease in mitotic markers including MPM-2 labeling and cyclin B1/cdc2 kinase activity. (aacrjournals.org)
  • Cyclin D combines with CDK4/6 and hyper-phophorylates pRB, which results in its dissociation in the E2F complicated therefore, permitting the transcription of key S phase advertising genes. (bcrablinhibitor.com)
  • [ 3 ] G1 progression is governed by D-type and E-type cyclin-cdk complexes. (medscape.com)
  • plosone.orgOne with the key events within the progression of the cells from G1 to S phase would be the activation of E2F-DP complex regulated by Cyclin-Cdk. (bcrablinhibitor.com)
  • The novel prophylactic and therapeutic approach deals especially the molecules involved in inflammation of cholangiocite or those related to promotion and progression of CC. The elucidation of their specific effects and interaction of this complex mechanism will accelerate the development of new biomarker for early detection and predictor factors outcome in CC. (gastrores.org)
  • In contrast to the reduction of cyclin D1 with cyclosporin A, ectopic expression of calcium/calmodulin-independent calcineurin promoted synthesis of cyclin D1 during G(1) progression. (duke.edu)
  • The various markers that enable assessment of the progression of preneoplastic lesions to spindle cell carcinoma include the p16 protein, which halts the cell cycle and induces apoptosis by pRb-mediated phosphorylation of cyclin-dependent kinase 4 (CDK4). (bvsalud.org)
  • The following product was used in this experiment: Cyclin D1 Monoclonal Antibody (3D8) from Thermo Fisher Scientific, catalog # MA5-15650, RRID AB_10978307. (thermofisher.com)
  • Mouse monoclonal antibody to CDK4. (biopaqc.com)
  • p27 phosphorylation by Akt impairs its nuclear import and leads to cytoplasmic p27 accumulation. (medscape.com)
  • Two multi-system disorders, Myotonic Dystrophies type 1 and type 2 (DM1 and DM2), are complex neuromuscular diseases caused by an accumulation of expanded, non-coding RNAs, containing repetitive CUG and CCUG elements. (nih.gov)
  • [3] Mitogenic signals received throughout G1-phase cause gradual accumulation of cyclin D, which complexes with CDK4/6. (wikipedia.org)
  • In contrast, pretreatment with flavopiridol prevents cells from entering mitosis by inhibiting cyclin B1/cdc-2 kinase activity, thus antagonizing the docetaxel effect. (aacrjournals.org)
  • In these studies we show that flavopiridol, a cyclin-dependent kinase inhibitor, potentiates docetaxel-induced apoptosis 3-fold in MKN-74 human gastric cells. (aacrjournals.org)
  • This structure of an authentic CDK/cyclin complex shows that cyclin binding may not be sufficient to drive the CDK active site toward an active conformation. (nih.gov)
  • 20. Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF. (nih.gov)
  • Cyclin D1 is a putative proto-oncogene overexpressed in a wide variety of human neoplasms including mantle cell lymphomas (MCL). (thermofisher.com)
  • The Cyclin D1 protein belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. (thermofisher.com)
  • Cyclin D1 has been successfully employed and is a promising tool for further studies in both cell cycle biology and cancer associated abnormalities. (thermofisher.com)
  • The p16INK4A protein is a cell-cycle inhibitor that acts by inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in the control of the cell cycle by phosphorylating Rb protein. (medscape.com)
  • In addition to a constitutively occupied E2F1-Sp1 site immediately upstream of the cyclin E transcription start region, there is downstream a cell cycle-regulated site (termed CERM) that may function as a cyclin E-repressor module. (nih.gov)
  • Regardless of cell type, the tumorigenic changes that drive cancer growth and metastasis are complex. (technologynetworks.com)
  • Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. (wuxibiortus.com)
  • We do not know the relevant set of substrates G1 cyclin-Cdk complexes target to drive the G1/S transition nor those that coordinate cell division with other processes such as metabolism, transcription, differentiation, the immune response, and DNA damage repair. (nih.gov)
  • Our previous work identified a novel helix-based docking mechanism for cyclin D, a key driver of cell cycle entry whose major target is the retinoblastoma protein Rb. (nih.gov)
  • Working in the lab of Mart Loog, he discovered how the arrangement of phosphorylation sites and cyclin docking sites together control multisite phosphorylation to determine the timing of protein activity through the cell cycle. (nih.gov)
  • The second part of his work found that intrinsic cyclin-Cdk activity increases for complexes expressed later in the cell cycle, while weak kinase activity of earlier expressed complexes is compensated by specific docking allowing them to target key subsets of Cdk targets early in the cell cycle. (nih.gov)
  • The cyclin box fold: protein recognition in cell-cycle and transcription control. (embl-heidelberg.de)
  • Oxidative phosphorylation is a common process to most organisms in which the main function is to generate an electrochemical gradient across the inner mitochondrial membrane (IMM) and to make energy available to the cell. (biomed.news)
  • Theactivity of this kinase is restricted to the G1-S phase, which is controlled by the regulatorysubunits D-type cyclins and CDK inhibitor p16(INK4a). (biopaqc.com)
  • Throughout M phase and G1 phase, cells assemble inactive pre-replication complexes (pre-RC) on replication origins distributed throughout the genome. (wikipedia.org)
  • thus cyclin - dependent kinase (CDK) must actively contribute to stationary phase establishment. (biologists.com)
  • To elaborate the molecular pathway of CDK4 activation and substrate selection we have determined the structure of nonphosphorylated CDK4/cyclin D3. (nih.gov)
  • We use quantitative biochemical and molecular biology approaches, successfully employed with yeast cyclins, to identify the full docking repertoire of mammalian cyclins. (nih.gov)
  • Cancer is a complex entity and regardless of cancer type, there are frequently observed cellular changes involved in tumorigenesis, tumor growth, and metastasis. (technologynetworks.com)
  • During a replicative cycle, CRK5 stably interacts with a single Plasmodium -specific cyclin (SOC2), although we obtained no evidence of SOC2 cycling by transcription, translation or degradation. (elifesciences.org)
  • C1 The Cyclin D1 promoter is activated by E2F4, but it is repressed by E2F1 via pRb (Watanabe et al. (nih.gov)
  • In addition, reduce inside the expression of E2F1 by piperine indicates repression of E2F complex. (bcrablinhibitor.com)
  • Bifurcation analysis helps to identify the key * components of this extremely complex interaction network. (nih.gov)
  • Solution structure of the C-terminal core domain of human TFIIB: similarity to cyclin A and interaction with TATA-binding protein. (embl-heidelberg.de)
  • the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity). (nih.gov)
  • This shows that upon launch through the contact-arrested condition, a temporal purchase for the reactivation of inactive p27-cyclin D-cdk4 complexes must can be found: p27 should be Y phosphorylated 1st, straight permitting cyclin H-cdk7 phosphorylation of residue T172 as well as the consequent repair of kinase activity. (azd1152.com)
  • Red No. 3, beta-estradiol, and DDT increase ER site-specific DNA binding to the estrogen response element in HTB 133 cells and increase cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells. (researchgate.net)
  • Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway. (wanfangdata.com.cn)
  • After binding the Cyclin in the PSTAIRE helix, the protein changes its conformational structure to expose the phosphorylation motif. (wikipedia.org)
  • Furthermore, our results show that rhHAPLN1 significantly inhibited the phosphorylation of FAK, AKT, STAT3, p38 MAPK and Raf mediated by the binding of PDGF-BB to PDGFRβ. (bmbreports.org)
  • HN - 2006(1981) BX - Cofilins MH - Actin-Related Protein 2 UI - D051377 MN - D5.750.78.730.246.500 MN - D12.776.220.525.246.500 MS - A PROFILIN binding domain protein that is part of the Arp2-3 complex. (nih.gov)
  • Because cyclin D1 mRNA was induced normally in the cyclosporin A-treated cells, we analyzed the half-life of cyclin D1 in the presence of cyclosporin A and found no difference from control cells. (duke.edu)
  • [6] NPAT is activated by phosphorylation and recruits the Tip60 chromatin remodeling complex to the promoters of histone genes. (wikipedia.org)
  • Taken together, these results suggest that the structural mechanism of CDK4/cyclin D3 activation differs markedly from that of previously studied CDK/cyclin complexes. (nih.gov)
  • We discovered a novel mechanism by which cyclin-Cdk complexes drive the G1/S transition in budding yeast. (nih.gov)
  • The discovery of this completely novel helix-based docking mechanism for cyclin-Cdk complexes revealed new possibilities for novel cancer therapies. (nih.gov)
  • 1997) . c-Abl-dependent phosphorylation of DNA-PK is stimulated by ionizing radiation (Kharbanda et al. (nih.gov)
  • 17. Changes in E2F complexes containing retinoblastoma protein family members and increased cyclin-dependent kinase inhibitor activities during terminal differentiation of cardiomyocytes. (nih.gov)
  • Recent studies have shown that while non-stem, bulk cancer cells utilize glycolysis, breast CSCs are more dependent on oxidative phosphorylation (OxPhos) and therefore targeting mitochondria may inhibit CSC function. (biomed.news)
  • We aimed to investigate whether there is an association between the cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) rs1333049 and zinc finger homeobox 3 (ZFHX3) rs2106261 single nucleotide polymorphisms (SNPs) and the degree of COVID-19 severity. (biomedcentral.com)
  • Cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) spans approximately 126.3 kb, overlaps with cyclin-dependent kinase inhibitor 2B (CDKN2B) (p15) at the 5´ end, comprises 20 exons that are prone to alternative splicing and is reported to be linked to CAD risk, hypertension (HTN) and stroke [ 13 ]. (biomedcentral.com)
  • The overarching aim of this study is to determine the docking mechanisms of mammalian cyclins. (nih.gov)
  • His second major finding revealed how cyclin D-Cdk4,6 complexes in mammalian cells drive the G1/S transition by targeting the retinoblastoma protein, Rb, through its most C-terminal helix. (nih.gov)
  • In WD/DDLPS, NCs contain amplified copies of genes including MDM2 , CDK4, SAS, HMGA2 and YEATS4, whose over-expression is thought to drive or contribute to carcinogenesis. (sarcomahelp.org)
  • p21 has also shown to be a component of active cyclin-cdk complexes, suggesting that p21-containing complexes may shift between active and inactive states through changes in p21 content. (bdbiosciences.com)
  • Active, p21-containing complexes appear to contain one p21 molecule, whereas inactive complexes contain multiple p21 molecules. (bdbiosciences.com)
  • Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by an E3 ligase such as PIAS1-4, RANBP2 or CBX4. (nih.gov)
  • 2. We do not know the extensive docking mechanisms different cyclin-Cdk complexes use to recognize this wide range of target substrates. (nih.gov)