• Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (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)
  • This team science approach has led to recent ground-breaking publications defining roles of new drug targets in Molecular Cell , Cancer Discovery , Genes & Development and Cell Chemical Biology . (fredhutch.org)
  • 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)
  • Wu M, Sun Y, Xu F, Liang Y, Liu H, Yi Y. Annexin A2 Silencing Inhibits Proliferation and Epithelial-to-mesenchymal Transition through p53-Dependent Pathway in NSCLCs. (jcancer.org)
  • The cyclin-dependent kinase inhibitor, p21 cip1/waf1 (p21), maintains hematopoietic stem cell quiescence, and we evaluated its role in the regenerative response of neural tissue after ischemic injury using the mice deficient in p21. (rupress.org)
  • Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have revolutionized the treatment of hormone-positive metastatic breast cancers (mBCs). (her2support.org)
  • Although CDK4/6 inhibitors have significant clinical benefits and enable physicians to delay starting chemotherapy, they are expensive and can be associated with drug toxicities. (her2support.org)
  • Here, we have performed a systemic review of the reported molecular markers predictive of drug response including intrinsic and acquired resistance for CDK4/6 inhibition in mBC. (her2support.org)
  • CDK4 is a member of the Ser/Thr protein kinase family. (thermofisher.com)
  • ST caused G0/G1 cell cycle arrest which was accompanied by a decrease in CDK4 and cyclin D1, and an increase in p21/Cip1and p27/Kip1 protein levels. (biomedcentral.com)
  • The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.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)
  • Cyclin-dependent kinase inhibitor 1C (p57, Kip2), also known as CDKN1C, is a protein which in humans is encoded by the CDKN1C imprinted gene. (wikipedia.org)
  • Cyclin-dependent kinase inhibitor 1C is a tight-binding inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. (wikipedia.org)
  • It encodes a cell cycle inhibitor that binds to G1 cyclin-CDK complexes. (wikipedia.org)
  • Cyclin E forms complexes during this interval with CDK2. (biomedcentral.com)
  • Cyclins and CDKs assemble into complexes with one another as cells progress through G1 phase, cyclins being required to activate the serine-threonine kinase activity of their catalytic partners. (biomedcentral.com)
  • The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (biomedcentral.com)
  • Transcriptional and translational control, sequestration in cyclin D1 complexes and localization all regulate p27 in G1 phase. (biomedcentral.com)
  • [ 2 ] Options for second-line therapy in patients with relapsed/refractory disease include chemotherapy-free regimens with biologic targeted agents such as covalent Bruton tyrosine kinase (BTK) inhibitors, lenalidomide,venetoclax, and chimeric antigen receptor (CAR) T-cell therapy. (medscape.com)
  • Up-regulation appears to be specific to p27 because expression of cyclin D1, E, and A, and p21Cip1/Waf1 was not modulated by these agents. (biomedcentral.com)
  • A vast amount of research exists on the possible molecular mechanisms through which vitamin D affects cancer cell proliferation, cancer progression, angiogenesis, and inflammation. (mdpi.com)
  • Understanding the molecular mechanisms underlying Al toxicity might contribute to improve strategies for prevention, early detection, and targeted therapies for the management of colon cancer patients. (bvsalud.org)
  • In recent years, molecular mechanisms of cell aging, their connection with oncological diseases and inflammation have been discovered. (vechnayamolodost.ru)
  • This review expounds the up- or down-regulation of lncRNAs in OSCC and the molecular mechanisms by which lncRNAs perform their function in the malignant cell. (biomedcentral.com)
  • In the present study, a bioinformatics approach was used to investigate the molecular mechanisms and prognosis of ACC. (cancerindex.org)
  • These results provide an insight into the potential molecular mechanisms regulating ruminal epithelial absorptive metabolism and growth following nutrient restriction and subsequent compensatory growth. (biomedcentral.com)
  • Aggressive tumors typically demonstrate a high glycolytic rate, which results in resistance to radiation therapy and cancer progression via several molecular and physiologic mechanisms. (springer.com)
  • Intriguingly, many of these mechanisms utilize the same molecular pathways that are altered through calorie and/or carbohydrate restriction. (springer.com)
  • PIK3CA mutation and loss of PTEN expression are being pursued as potential predictors of response to novel PI3K pathway inhibitors. (aacrjournals.org)
  • Assay of the mutants with a cyclin-dependent kinase 4-selective bisanilinopyrimidine shows that the K89T mutation is primarily responsible for the selectivity of this compound. (rcsb.org)
  • The new inhibitor is 1,000-fold more potent than the parent compound (K(i) values for CDK1 = 9 nM and CDK2 = 6 nM versus 5,000 nM and 12,000 nM, respectively, for O(6)-cyclohexylmethylguanine). (rcsb.org)
  • The increased potency arises primarily from the formation of two additional hydrogen bonds between the inhibitor and Asp 86 of CDK2, which facilitate optimum hydrophobic packing of the anilino group with the specificity surface of CDK2. (rcsb.org)
  • The work represents the first successful iterative synthesis of a potent CDK inhibitor based on the structure of fully activated CDK2-cyclin A. Furthermore, the potency of O(6)-cyclohexylmethyl-2-(4'- sulfamoylanilino)purine was both predicted and fully rationalized on the basis of protein-ligand interactions. (rcsb.org)
  • The cytomorphology of each sample was reviewed and BAP1 IHC and Cyclin-dependent kinase inhibitor 2A gene (CDKN2A) fluorescence in situ hybridisation investigations (FISH) were performed. (edu.au)
  • Five out of eight cases (63%) displayed cyclin-dependent kinase inhibitor 2A (CDKN2A) abnormalities, either copy number loss (n = 4) or truncating mutations (n = 1). (lu.se)
  • In particular, the p16/cyclin-dependent kinase inhibitor 2A (CDKN2A) gene located on chromosomal region 9p21 frequently is altered in several types of cancer. (iiarjournals.org)
  • The tumor suppressor gene p16/cyclin-dependent kinase inhibitor-2A (CDKN2A) is located within the chromosomal region 9p21 and encodes a cell-cycle protein that is an inhibitor of cyclin-dependent kinases (CDK)-4 and -6. (iiarjournals.org)
  • Molecular and Cellular Biology, 30, 1217-1230. (uri.edu)
  • Last week I bumped into a colleague who teaches in our third year molecular biology course. (blogspot.com)
  • Plant Molecular Biology 71, 307-318. (helsinki.fi)
  • Molecular Biology and Evolution , 21 (3), 555-562. (ncsu.edu)
  • PCNA is a co-factor of cyclin-D and it makes a complex with cyclin-D, a cyclin dependent kinase (CDK), and a cyclin dependent kinase inhibitor (CDKI). (biomedcentral.com)
  • Basal levels of phospho-Ser 6 inhibitor-1, as detected by a phosphorylation state-specific antibody against the site, existed in specific regions of the brain and varied with age. (elsevierpure.com)
  • As a result, it negatively regulates cyclin-D-dependent phosphorylation of the retinoblastoma (pRb) gene product, thus blocking cell-cycle progression from G 1 -to S-phase ( 2 - 4 ). (iiarjournals.org)
  • This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). (thermofisher.com)
  • Because the identification of key histopathologic features is highly sensitive to sampling, the new guidelines recommend using molecular signatures-which tend to be more diffuse and thus less sensitive to sampling-as a component in grading certain tumors and as a potential marker of clinical course and prognosis. (medscape.com)
  • Hypoxia and genetic defects that chronically drive proliferation leave such tumors dependent on a steady supply of nutrients, especially glucose. (springer.com)
  • Inhibitor-1, the first identified endogenous inhibitor of protein phosphatase 1 (PP-1), was previously reported to be a substrate for cyclin-dependent kinase 5 (Cdk5) at Ser 67 . (elsevierpure.com)
  • Thus, inhibitor-1 serves as a critical junction between kinase- and phosphatase-signaling pathways, linking PP-1 to not only PKA and calcineurin but also Cdk5. (elsevierpure.com)
  • The detection of HPV DNA alone, in the absence of evidence for viral gene expression, is not unequivocal molecular evidence that HPV infection either causes or promotes malignant progression in a lesion. (biomedcentral.com)
  • There are few studies focusing on the molecular analysis of p16 gene in ovarian cancer ( 13 - 16 ). (iiarjournals.org)
  • Up-regulation of the expression of p27 is likely due to the activation of translation rather than transcription of p27 because (a) up-regulation is mediated by the 5'-untranslated region (-575) of the p27 gene and (b) the antibiotic actinomycin D, an inhibitor of transcription, did not attenuate the up-regulation of p27. (biomedcentral.com)
  • Association between cyclin-dependent kinase inhibitor 2B antisense RNA 1 and zinc finger homeobox 3 gene polymorphisms and COVID-19 severity. (cdc.gov)
  • The molecular consequence of translocation is overexpression of the protein cyclin D1 (coded by the PRAD1 gene located close to the breakpoint). (medscape.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)
  • In conclusion, this study provides the first evidence of Al bioaccumulation in colon cancer and its potential role in modulating molecular pathways involved in cancer progression, such as EMT and apoptosis. (bvsalud.org)
  • A small-molecule inhibitor of RAD51reduces homologous recombination and sensitizes multiple myeloma cells to doxorubicin. (advancingcures.org)
  • Human Molecular Genetics, 14, 693-701. (uri.edu)
  • Regulation of the activation of the Fanconi anemia pathway by the p21 cyclin-dependent kinase inhibitor. (uri.edu)
  • Cyclin dependent kinases are a key family of kinases involved in cell cycle regulation and are an attractive target for cancer chemotherapy. (rcsb.org)
  • In this publication, the authors took a medicinal chemistry approach to identify an inhibitor for cyclin-dependent kinase 11 (CDK11), an understudied protein with important roles in cell cycle regulation, neuronal function and cell death. (fredhutch.org)
  • Molecular markers might predict disease progression and behaviour more accurately than the available prognostic factors. (ox.ac.uk)
  • Reprogramming techniques continue to evolve as we learn more about the developmental and molecular cues which govern cellular differentiation and identity. (silverchair.com)
  • The cyclin-dependent kinase (Cdk) inhibitor p21Cip1 (p21) plays a crucial role in restraining cellular proliferation and maintaining cellular quiescence. (blogspot.com)
  • p27(Kip1) is a cyclin-dependent kinase inhibitor. (biomedcentral.com)
  • The cyclin-dependent kinase (CDK) inhibitor p27(Kip1) is a key cell-cycle regulator of G1-to-S phase transition [ 1 ]. (biomedcentral.com)
  • The rapidly emerging molecular landscape is captured through next-generation sequencing of breast cancers (DNA with or without RNA), liquid biopsies (circulating tumor DNA), and protein analyses. (her2support.org)
  • Use of the cyclin-dependent kinase 2-selective 6-cyclohexylmethoxy-2-(4'-sulfamoylanilino)purine (NU6102) shows that K89T has no role in the selectivity, while the remaining three mutations have a cumulative influence. (rcsb.org)
  • Classification of astrocytomas is based on distinct histopathologic and molecular alterations, and drives treatment decision making. (medscape.com)
  • In more recent years ancillary tests based on the common molecular alterations in the disease have become more widely available to pathologists. (edu.au)
  • Therefore, detectable molecular alterations were identifiable in seven of eight initial samples prior to the development of cytomorphological features diagnostic of mesothelioma. (edu.au)
  • Our findings pinpoint clinically relevant alterations, which may indicate response to CDK inhibitors, and focal hypermutational phenotypes that may be coupled to improved responses using immune checkpoint inhibitors. (lu.se)
  • This study provides valuable insight into the chemopreventive efficacy and associated molecular alterations of ST in breast cancer cells whereas it had only moderate efficacy on lung cancer cells and did not show any considerable effect on skin cancer cells. (biomedcentral.com)
  • We assessed whether cell cycle inhibitors that restrict stem cell populations in other tissues may participate in limiting neural stem cell reactivity in vivo. (rupress.org)
  • In vivo, chronic treatment with the non-selective antidepressant imipramine as well as the norepinephrine-selective reuptake inhibitor desipramine or the serotonin-selective reuptake inhibitor fluoxetine all decrease p21 expression, and this was associated with increased neurogenesis. (blogspot.com)
  • 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)
  • Second, as FA is unequivocally linked to both hematologic and non-hematologic cancer susceptibility, our findings will provide important mechanistic insight in to the molecular origins of cancer susceptibility in the general (non-FA) population. (uri.edu)
  • Metformin (MTF) has been reported to target NLK (Nemo-like kinase) to inhibit non-small lung cancer cells. (cancerindex.org)
  • Molecular markers nowadays seem to have the potential to improve our ability to care for patients with, or at risk for, breast cancer. (biomedcentral.com)
  • Background: The molecular events leading to the development of ovarian cancer are not well-established. (iiarjournals.org)
  • The molecular events leading to the development of ovarian cancer and the molecular factors that may predict response to treatment are not well-established. (iiarjournals.org)
  • While exploring the molecular changes associated with strong ST efficacy in breast cancer cells, we observed that ST induced cell cycle arrest as well as cell death. (biomedcentral.com)
  • Toward the goal of developing new treatments for osteosarcoma, Fu and colleagues show apoptosis of osteosarcoma cells by SCH 727965 (SCH), a new cyclindependent kinase inhibitor. (aacrjournals.org)
  • Chronic antidepressant treatment did not affect the expression of other Cdk inhibitors. (blogspot.com)
  • These results demonstrate the unique role of p21 in the control of neurogenesis, and support the hypothesis that different classes of reuptake inhibitor-type antidepressant drugs all stimulate hippocampal neurogenesis by inhibiting p21 expression. (blogspot.com)
  • Similarly, depletion in the STRIPAK component STRIP1 affects activation of GCKIII kinases and cell cycle disruption through elevated expression of cyclin dependent kinase inhibitors p21 and p27, enhanced levels of which lead to a protective effect from therapeutic treatments and increased proliferation. (lu.se)
  • This review article describes the current theories regarding the pathogenesis and molecular evolution of these lesions. (biomedcentral.com)
  • The aim of this review article is to describe the current theories regarding the pathogenesis and molecular evolution of preinvasive breast lesions. (biomedcentral.com)
  • Therefore, tissue diagnosis with histological and molecular characterization is essential. (medscape.com)
  • The use of molecular markers in the common clinical practice seems promising for the diagnosis and prognostication. (biomedcentral.com)
  • Therefore, p21 is an intrinsic suppressor to neural regeneration after brain injury and may serve as a common molecular regulator restricting proliferation among stem cell pools from distinct tissue types. (rupress.org)
  • Molecular docking analysis revealed that PPI exhibited a higher binding affinity with GRP78. (bvsalud.org)
  • [ 2 ] Grade was applied across tumor types, regardless of differences in the clinical course and molecular behavior of different anaplastic tumor entities. (medscape.com)
  • [ 3 ] Consequently, grading each tumor requires an integrated analysis of histologic features and molecular signatures specific to that tumor type. (medscape.com)
  • It was identified that the nuclear division cycle 80, cyclin B2 and topoisomerase 2‑α may serve important roles in adrenocortical tumor development. (cancerindex.org)
  • The evaluation of molecular markers is performed under the light of their potential usefulness in treatment decisions presenting in the common clinical practice. (biomedcentral.com)
  • Dephosphorylation of inhibitor-1 at Thr 35 is equivalent to inactivation of the protein, as inhibitor-1 only serves as an inhibitor of PP-1 when phosphorylated by cAMP-dependent kinase (PKA) at Thr 35 . (elsevierpure.com)
  • DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)