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  • melanoma
  • A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. (springer.com)
  • Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. (springer.com)
  • Defects in CDK4 are a cause of susceptibility to cutaneous malignant melanoma type 3 (CMM3) [MIM: (abcam.com)
  • Pigment Cell Melanoma Res. (wikipedia.org)
  • bind
  • Cyclin D proteins bind to enzymes called CDK4/6 and together they form heterodimers. (springer.com)
  • Mitogenic growth factors bind to their cognate receptors and initiate a cascade of events that culminate in the expression and assembly of different kinase holoenzymes composed of a regulatory. (springer.com)
  • Within the nucleus, MyoD can bind to the G1 cyclin-dependent kinase, cdk4. (cancer.gov)
  • In addition to this structural similarity the "Cip/Kip" proteins share the functional characteristic of being able to bind several different classes of Cyclin and Cdk molecules. (wikipedia.org)
  • This occurs when p27 is phosphorylated on Ser(10) which allows for CRM1, a nuclear export carrier protein, to bind to and remove p27 from the nucleus. (wikipedia.org)
  • Should an oncogenic protein, such as those produced by cells infected by high-risk types of human papillomaviruses, bind and inactivate pRb, this can lead to cancer. (wikipedia.org)
  • nucleus
  • The protein can be found in the cytoplasm and the nucleus, however most of the active complexes are found in the nucleus of proliferating cells. (wikipedia.org)
  • During the G1 phase, it is synthesized rapidly and accumulates in the nucleus, and is degraded as the cell enters the S phase. (wikipedia.org)
  • These Ras-mediated pathways lead to the increase in transcription of cyclin D1, and inhibit its proteolysis and export from the nucleus. (wikipedia.org)
  • Cyclin D1 is degraded in response to reduced levels of growth factors and mitogens, and consequently cdk4 remains in the cytoplasm, allowing MyoD to remain unbound and active within the nucleus. (cancer.gov)
  • pathways
  • Emerging evidence suggests that miRNAs regulate critical pathways involved in stem cell function. (springer.com)
  • Additionally, non-protein-coding gene-regulatory elements may also influence these signaling pathways, and screening for these is also highly amenable to high-throughput methods. (aacrjournals.org)
  • It is apparent that the order and timing of the cell cycle is critical for accurate transmission of genetic information, and consequently, a number of biochemical pathways have evolved to ensure that initiation of a particular cell cycle event is dependent on the accurate completion of another. (springer.com)
  • Molecular Pathways: targeting the cyclin D-CDK4/6 axis for cancer treatment. (springer.com)
  • Increasing cyclin D1 levels during the G1 phase is induced by mitogenic growth factors primarily through Ras mediated pathways, and hormones. (wikipedia.org)
  • The major signaling pathways that give rise to the phenotype of these cells may serve as a good resource of information when researchers in drug discovery and development use these cells to identify novel targets and biomarkers. (hindawi.com)
  • Major signaling pathways and mutations affecting the coding sequence are also described providing important information when using these cells as a model in a variety of studies. (hindawi.com)
  • New technologies such as next generation sequencing have enabled molecular characterization and identification of signaling pathways in specific cell lines. (hindawi.com)
  • Cyclin D is regulated by the downstream pathway of mitogen receptors via the Ras/MAP kinase and the β-catenin-Tcf/LEF pathways and PI3K. (wikipedia.org)
  • 2017
  • As of early 2016, abemaciclib is involved in 3 Phase III clinical trials: The JUNIPER Study is comparing abemaciclib against erlotinib in patients with stage IV non-small-cell lung carcinoma Due to collect data until September 2017. (wikipedia.org)
  • Xenopus
  • Since its initial discovery, homologues of cyclin A have been identified in numerous eukaryotes including Drosophila, Xenopus, mice, and in humans but has not been found in lower eukaryotes like yeast. (wikipedia.org)
  • A single cyclin A gene has been identified in Drosophila while Xenopus, mice and humans contain two distinct types of cyclin A: A1, the embryonic-specific form, and A2, the somatic form. (wikipedia.org)
  • accumulation
  • Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. (wikipedia.org)
  • Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases, cardiovascular diseases, inflammatory responses and autoimmune diseases, and systemic DNA damage responses leading to malignancies. (wikipedia.org)
  • In proliferating cells, cyclin D-Cdk4/6 complex accumulation is of great importance for cell cycle progression. (wikipedia.org)
  • Positive feed-back loops include G1 cyclins and accumulation of E2F. (wikipedia.org)
  • initiation
  • It is also suggested that a certain type of stem-like cells is responsible for the initiation of cancer, so-called cancer stem cells (CSCs). (springer.com)
  • differentiation
  • He demonstrated that tissue-specific microRNA regulatory networks buffer gene function critical to cell homeostasis and differentiation, where the disruption of either can lead to cell transformation and cancer. (cancer.gov)
  • Terminal differentiation is marked by the withdrawal of the myoblast from the cell cycle. (cancer.gov)
  • MyoD is a protein that plays a major role in regulating muscle differentiation. (wikipedia.org)
  • vivo
  • Human tumor-derived cell lines grown in vitro and in vivo are important models to study cancer development, progression, and therapeutic response and resistance to anticancer drugs. (hindawi.com)
  • thus
  • As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury, ventricular hypertrophy and Heart failure. (wikipedia.org)
  • Retinal cells are not sloughed off or replaced, and are subjected to high levels of mutagenic UV radiation, and thus most pRB knock-outs occur in retinal tissue (but it's also been documented in certain skin cancers in patients from New Zealand where the amount of UV radiation is significantly higher). (wikipedia.org)
  • Thus MyoD enhances its own activity in the cell in a feedforward manner. (wikipedia.org)