• Recent studies have shown that cyclin-dependent kinase (CDK) inhibitors can have a tremendous impact on cell cycle progression in plants. (uni-bielefeld.de)
  • Survivin belongs to the family of inhibitors of apoptosis proteins (IAPs) that plays a pivotal role in mitotic progression, apoptosis inhibition, angiogenesis, progression of cancer, and invasion [ 5 ]. (springeropen.com)
  • Small molecule inhibitors designed to target the DNA damage sensors, such as inhibitors of ataxia telangiectasia-mutated (ATM), ATR, CHK1 and WEE1, impair smooth cell cycle modulation and disrupt efficient DNA repair, or a combination of the above, have demonstrated interesting monotherapy and combinatorial activity, including the potential to reverse drug resistance and have entered developmental pipelines. (bmj.com)
  • 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)
  • During cell-cycle progression, substrates of a single master regulatory enzyme can be modified in a specific order. (biomedcentral.com)
  • Progression through the cell cycle is accompanied by dramatic changes in cellular content and behavior, and involves a large number of proteins and processes. (biomedcentral.com)
  • This ordering of substrate modification allows a small number of master regulators to carry out their functions over a large time window with high temporal resolution, enabling precise and robust control of the numerous processes underlying cell cycle progression [ 1 , 2 ]. (biomedcentral.com)
  • The APC/C is an E3 ubiquitin ligase that drives mitotic progression by promoting timely degradation of key regulatory proteins [ 3 ]. (biomedcentral.com)
  • The activator Cdc20 is then replaced by a second activator, Cdh1, and APC/C Cdh1 promotes complete degradation of M cyclin, followed by polo-like kinase 1, Aurora A, and other substrates, to complete mitosis and cytokinesis and drive progression into G1 [ 1 , 2 ]. (biomedcentral.com)
  • In the presence of errors or damage during DNA replication, cell cycle checkpoint nodes and repair machinery work in concert to retard cell cycle progression until sufficient repair has been achieved. (bmj.com)
  • During cell growth and proliferation, ubiquitin plays an outsized role in promoting progression through the cell cycle. (intechopen.com)
  • While several studies addressed how cell motility parameters change throughout the cell cycle, the relationship between invadopodia and cell cycle progression has not been elucidated. (biorxiv.org)
  • 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)
  • Taken together, these findings suggest that invadopodia function is tightly linked to cell cycle progression and is controlled by specific cell cycle regulators. (biorxiv.org)
  • Cell cycle progression is governed by a complex network of cyclin-dependent kinases that define not only the phase of the cell cycle, but also the timing of transitions between phases 13 . (biorxiv.org)
  • It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (thermofisher.com)
  • Mutations, amplification and overexpression of this gene, which alters cell cycle progression, are observed frequently in a variety of tumors and may contribute to tumorigenesis. (genetex.com)
  • Mutations, amplification and overexpression of this gene, which alters cell cycle progression, are observed frequently in a variety of human cancers. (ayassbioscience.com)
  • We combined time-lapse microscopy, highly multiplexed single-cell imaging of 48 core cell cycle proteins, and manifold learning to render a visualization of the human cell cycle. (bvsalud.org)
  • We show that cyclin-dependent kinase (CDK) consensus motifs are frequently clustered in CDK substrate proteins. (biomedcentral.com)
  • We also show that human CDK targets are enriched for proteins that contain clustered consensus matches and, by searching human cell cycle genes, we predict several putative CDK targets, including the human orthologs of Schizosaccharomyces pombe CDC5 (CDC5L) and S. cerevisiae Cdc20p (CDC20). (biomedcentral.com)
  • The presence of replication stress activates the DNA damage response and downstream checkpoint proteins including ataxia telangiectasia and Rad3 related kinase (ATR), checkpoint kinase 1 (CHK1), and WEE1-like protein kinase (WEE1), which trigger cell cycle arrest while protecting and restoring stalled replication forks. (bmj.com)
  • Any obstacles encountered by cells in this process can lead to 'replicative stress' ( Figure 1 ), 1 which may be overcome by replicative stress response proteins, but deficiencies in this response result in accumulated errors in DNA replication and loss of genomic integrity, which lead to cell death. (bmj.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)
  • Invadopodia are cancer cell protrusions rich in structural proteins (e.g. (biorxiv.org)
  • Transcripts found in unfertilized oocytes also encoded a large number of proteins implicated in cell adherence, tight junction and focal adhesion, suggesting high complexity in terms of structure and cellular interactions in embryos prior to midblastula transition (MBT). (biomedcentral.com)
  • The oocyte is loaded with maternal mRNAs and proteins that control the cell maintenance and fate and the formation of the body plan prior to the onset of zygotic genome expression [ 3 , 4 ]. (biomedcentral.com)
  • 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)
  • CDK4 is a member of the Ser/Thr protein kinase family. (thermofisher.com)
  • These effects were associated with inhibition of the mitogen‑activated protein kinase/extracellular signal‑regulated kinase 1/2 and protein kinase B signaling pathways. (spandidos-publications.com)
  • The underlying mechanisms of these effects were primarily mediated by G 1 phase cell cycle arrest and inhibition of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulate kinase 1/2 (Erk 1/2) and protein kinase B (Akt) signaling pathways. (spandidos-publications.com)
  • This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. (wikipedia.org)
  • Cyclins function as regulators of cyclin-dependent kinases. (wikipedia.org)
  • Cyclins function as regulators of CDK kinases. (novusbio.com)
  • Our studies provide a conceptual framework for understanding how ordered modification can be established among substrates of the same regulatory enzyme, and facilitate our understanding of how precise temporal control is achieved by a small number of master regulators to ensure a successful cell division cycle. (biomedcentral.com)
  • Microarray analyses detected a suite of master developmental regulators that control differentiation and maintenance of diverse cell lineages. (biomedcentral.com)
  • Dysregulation of CDK8 (Cyclin-Dependent Kinase 8) and its regulatory partner CycC (Cyclin C) , two subunits of the conserved Mediator (MED) complex, have been linked to diverse human diseases such as cancer. (sdbonline.org)
  • In mitotic metaphase, typically the chromosomes (each with 2 sister chromatid that they developed due to replication in the S phase of interphase) arranged and sister chromatids split and distributed towards daughter cells. (mathisfunforum.com)
  • These chains are recognized by the proteasome, leading to substrate degradation [ 11 ]. (biomedcentral.com)
  • Among the diverse signaling outcomes associated with ubiquitination, the most well-established is the targeted degradation of substrates via the proteasome. (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 kinase complex is able to phosphorylate CDK2 and CDC2 kinases, thus functions as a CDK-activating kinase (CAK). (novusbio.com)
  • Finally, we examine co-clustering of the CDK consensus motifs with the 'cy' or RXL motif [ 17 ], which is known to be important in determining which CDK-cyclin complex will phosphorylate a given substrate. (biomedcentral.com)
  • Immunocytochemistry/ Immunofluorescence: Cyclin H Antibody (1B8) [H00000902-M01] - Analysis of monoclonal antibody to CCNH on HeLa cell. (novusbio.com)
  • Immunohistochemistry-Paraffin: Cyclin H Antibody (1B8) [H00000902-M01] - Analysis of monoclonal antibody to CCNH on formalin-fixed paraffin-embedded human testis. (novusbio.com)
  • Western Blot: Cyclin H Antibody (1B8) [H00000902-M01] - CCNH monoclonal antibody (M01), clone 1B8 Analysis of CCNH expression in HeLa. (novusbio.com)
  • Sandwich ELISA: Cyclin H Antibody (1B8) [H00000902-M01] - Detection limit for recombinant GST tagged CCNH is approximately 1ng/ml as a capture antibody. (novusbio.com)
  • Antibody reactivity against cell lysate and recombinant protein for WB. (novusbio.com)
  • WB analysis of HeLa cell lysate using GTX33611 Cyclin D1 antibody [RM241]. (genetex.com)
  • IHC-P analysis of human tonsil tissue using GTX33611 Cyclin D1 antibody [RM241]. (genetex.com)
  • There are currently no references for Cyclin D1 antibody [RM241] (GTX33611) . (genetex.com)
  • Here, we used experimental and computational approaches to dissect the quantitative mechanisms underlying the ordered degradation of the substrates of the ubiquitin ligase APC/C Cdc20 , a key regulator of chromosome segregation in mitosis. (biomedcentral.com)
  • Depending on how APC/C Cdc20 is partitioned among its substrates, competition can have minor or major effects on the degradation of certain substrates. (biomedcentral.com)
  • The degradation timing of APC/C Cdc20 substrates depends on the multi-step nature of ubiquitination, differences in substrate-APC/C Cdc20 interactions, and competition among substrates. (biomedcentral.com)
  • Protein kinases are critical to cellular signalling and post-translational gene regulation, but their biological substrates are difficult to identify. (biomedcentral.com)
  • MT1-MMP) and are responsible for degradation of the extracellular matrix (ECM). (biorxiv.org)
  • Metastasis is a complex, multi-step process that is initiated when cancer cells in the primary tumor acquire invasive properties, including motility and the ability to breakdown the extracellular matrix (ECM) 1 , and is responsible for the majority of cancer-related mortalities 2 . (biorxiv.org)
  • Mechanistically, the CHD4M195I protein showed augmented affinity to endocardial BRG1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4). (bvsalud.org)
  • Tumor cell invasion and metastasis require cancer cells to be both proliferative and invasive, i.e. migrate through the tissue and assemble invadopodia. (biorxiv.org)
  • However, under these microenvironmental conditions, only 15% of tumor cells assemble invadopodia at any given time, while the rest are non-motile. (biorxiv.org)
  • Protein kinases are ubiquitous components of cellular signalling networks [ 1 ]. (biomedcentral.com)
  • which divides the cytoplasm, organelles and cell membrane of one cell into two new cells containing roughly equal shares of these cellular components. (mathisfunforum.com)
  • In breast cancer, the cellular structures responsible for ECM degradation are invadopodia. (biorxiv.org)
  • This is the multihit theory of tumorigenesis, in which a series of multiple triggering events in the genetic and cellular makeup of a cell ultimately cause cancer. (medscape.com)
  • This data-driven approach revealed the comprehensive "structure" of the cell cycle: a continuum of molecular states that cells occupy as they transition from one cell division to the next, or as they enter or exit cell cycle arrest. (bvsalud.org)
  • In a quiescent state, it negatively regulates cell proliferation through the inhibition of the G1 to S phase transition to allow repair of DNA damages [ 7 ]. (springeropen.com)
  • 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)
  • In a number of animal species, MZT roughly coincides with the mid-blastula transition (MBT) [ 20 ] when cells become motile and divide asynchronously. (biomedcentral.com)
  • Localization to the chromocenters is mediated by an N-terminal domain, in addition we find that this domain may be involved in cyclin binding. (uni-bielefeld.de)
  • Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (wikipedia.org)
  • We previously demonstrated that invasive cells oscillate between two distinct states, termed the Invadopodia state and the Migration state 10 . (biorxiv.org)
  • They participate in two different transcriptional regulation processes, suggesting an important link between basal transcription control and the cell cycle machinery. (novusbio.com)
  • Besides CDK8 and CycC, further analyses of other subunits of the MED complex have revealed six additional subunits that are required for Mad-dependent transcription in the wing discs: Med12, Med13, Med15, Med23, Med24, and Med31. (sdbonline.org)
  • These results suggest that CDK8 and CycC, together with a few other subunits of the MED complex, may coordinate with other transcription cofactors in regulating Mad-dependent transcription during wing development in Drosophila. (sdbonline.org)
  • Securin degradation then unleashes separase to promote sister-chromatid separation. (biomedcentral.com)
  • It is expressed in cancer cells during the G2/M phase of the cell cycle and counteracts apoptosis activation during mitosis by interfering with caspase activity [ 6 ]. (springeropen.com)
  • In addition, cell cycle distribution analysis revealed that G0/G1 phase arrest was induced following pristimerin treatment in CAL‑27 and SCC‑25 cells, which was strongly associated with upregulation of p21 and p27, coupled with downregulation of cyclin D1 and cyclin E. Meanwhile, pristimerin induced significant apoptosis of CAL‑27 and SCC‑25 cells, alongside decreased levels of caspase‑3 and specific cleavage of poly (ADP‑ribose) polymerase. (spandidos-publications.com)
  • P27 is inactivated in cancer cells by various mechanisms including impaired synthesis, accelerated degradation, and mislocalization. (springeropen.com)
  • Maintaining genomic integrity is of utmost importance to eukaryotic cells, which have evolved sophisticated mechanisms to ensure speed, accuracy, and an adequate pool of nucleotide and replication factors as well as high-fidelity repair pathways to correct errors occurring during DNA replication. (bmj.com)
  • however, the antitumor effects and underlying mechanisms of pristimerin in oral cancer cells have not yet been identified. (spandidos-publications.com)
  • [ 6 ] These events lead the cancer cell to escape normal cell growth and control mechanisms, to avoid system control mechanisms (ie, immunologic surveillance), and to establish a nutrient supply. (medscape.com)
  • Knockout studies of the homologous gene in mouse suggest the essential roles of this gene in ovarian granulosa and germ cell proliferation. (wikipedia.org)
  • Survival, growth, and proliferation of malignant cells are affected by changes in both pro-apoptotic and anti-apoptotic signaling pathways. (springeropen.com)
  • Notably, the G1/S boundary represents a major barrier to cell proliferation and is universally dysfunctional in cancer cells, allowing for the unbridled proliferation observed in malignancy. (intechopen.com)
  • Results demonstrated that pristimerin was toxic against the two cell lines, and exhibited inhibitory effects against proliferation. (spandidos-publications.com)
  • The Invadopodia state is characterized by cell stasis and the presence of invadopodia, whereas the Migration state is defined by cell translocation and the absence of invadopodia. (biorxiv.org)
  • In the present study, the anticancer potential of pristimerin was investigated in two oral squamous cell carcinoma (OSCC) cell lines, CAL‑27 and SCC‑25. (spandidos-publications.com)
  • Because it is very invasive, the prognosis of oral squamous cell carcinoma (OSCC) is poor ( 5 ). (spandidos-publications.com)
  • An image depicting head and neck squamous cell carcinoma in vitro can be seen below. (medscape.com)
  • Head and neck squamous cell carcinoma in vitro (cell culture). (medscape.com)
  • This cyclin forms a complex with CDK7 kinase and ring finger protein MAT1. (novusbio.com)
  • The divisome is a protein complex in bacteria that is responsible for cell division, constriction of inner and outer membranes during division, and peptidoglycan (PG) synthesis at the division site. (mathisfunforum.com)
  • The different stages of mitosis all together define the mitotic (M) phase of an animal cell cycle-the division of the mother cell into two genetically identical daughter cells. (mathisfunforum.com)
  • Mutations/deletions in separate genes, each of which alone causes a minimal phenotype, but when combined in the same cell results in a more severe fitness defect or lethality under a given condition. (thebiogrid.org)
  • Numerous genes transcribed in oocytes are involved in multiple aspects of cell maintenance and protection, including metabolism, signal perception and transduction, RNA processing, cell cycle, defense against pathogens and DNA damage. (biomedcentral.com)
  • In this study, using invadopodia- and cell cycle- fluorescent markers, we show in 2D and 3D cell cultures, as well as in vivo , that breast carcinoma cells assemble invadopodia and invade into the surrounding ECM preferentially during the G1 phase of the cell cycle. (biorxiv.org)
  • Furthermore, this analyses confirmed the positive roles of CDK9 and Yorkie in regulating Mad-dependent gene expression in vivo. (sdbonline.org)
  • Before division can occur, the genomic information that is stored in chromosomes must be replicated, and the duplicated genome must be separated cleanly between cells. (mathisfunforum.com)
  • This degradation is mediated by at least two domains indicating the presence of at least two different pathways impinging on ICK1/KRP1 protein stability. (uni-bielefeld.de)
  • This dynamic oscillatory behavior is regulated by the activity of ECM receptor integrin β1, which determines the length of time a cell spends in each state. (biorxiv.org)
  • Furthermore, pristimerin exhibited a more potent anti‑proliferative activity in CAL‑27 and SCC‑25 cells than the common chemotherapy drugs cisplatin and 5‑fluorouracil. (spandidos-publications.com)
  • In this study, by comparing the activity of normal cell lines and cancer cell lines after treating with resveratrol, it was found that resveratrol has more significant cytotoxicity in cancer cell lines. (mdpi.com)
  • Cancer is characterized by uncontrolled growth and division of a cell, with extension beyond the normally limiting basement membrane and through the boundaries of normal cells. (medscape.com)
  • This cyclin and its kinase partner are components of TFIIH, as well as RNA polymerase II protein complexes. (novusbio.com)
  • Divisome and elongasome complexes responsible for peptidoglycan synthesis during lateral cell-wall growth and division. (mathisfunforum.com)
  • Pristimerin has also been reported to induce apoptosis of various human cancer cells, including in multiple myeloma ( 10 ), breast ( 11 ), liver ( 12 ), pancreatic ( 13 ) and prostate cancer ( 14 ). (spandidos-publications.com)
  • Pristimerin exhibited potent anti-proliferative and apoptosis-inducing effects on the OSCC cell lines CAL-27 and SCC-25. (spandidos-publications.com)
  • Resveratrol could play a toxic role through inducing apoptosis of the cancer cell in a time- and concentration-dependent manner. (mdpi.com)
  • Our results caution that this coordination between invasion and cell cycle must be considered when designing effective chemotherapies. (biorxiv.org)
  • Today, it is generally thought that the combination of determinants deposited by the mother during oogenesis and the inductive signals between different cells trigger the specification of different cell lineages during development of the embryo [ 7 , 8 ]. (biomedcentral.com)
  • We show experimentally that increased expression of the early APC/C Cdc20 substrate Clb5 does not delay the degradation of the later substrate securin, arguing against a role for competition with Clb5 in establishing securin degradation timing. (biomedcentral.com)
  • Understanding the organization of the cell cycle has been a longstanding goal in cell biology. (bvsalud.org)
  • The primary concern of cell division is the maintenance of the original cell's genome. (mathisfunforum.com)
  • Degradation of maternal transcripts and zygotic genome activation is characterized by striking changes in the transcriptome profiles. (biomedcentral.com)
  • The human body experiences about 10 quadrillion cell divisions in a lifetime. (mathisfunforum.com)
  • This technologic and biologic revolution continued through the 1960s to today, and the explosion in technology has fueled the current expansion of knowledge into the working of the human cell. (medscape.com)
  • Prokaryotes (bacteria and archaea) usually undergo a vegetative cell division known as binary fission, where their genetic material is segregated equally into two daughter cells. (mathisfunforum.com)
  • Because of its mutated aggressive genetics, this cell has a selective growth advantage over its neighbors. (medscape.com)