AURKA, CHK1 and PLK1 were identified as most promising targets and validated further in a more comprehensive panel of chondrosarcoma cell lines. Dose response curves were performed using tyrosine kinase inhibitors: MK-5108 (AURKA), LY2603618 (CHK1) and Volasertib (PLK1) using viability assays and cell cycle analysis Arid1a regulates cell cycle exit of transit-amplifying cells through inhibiting the Aurka-Cdk1 axis in mouse incisor Jiahui Du1,2, Junjun Jing1, Shuo Chen1, Yuan Yuan1, Jifan Feng1, Thach-Vu Ho1, Prerna Sehgal1, Jian Xu1, Xinquan Jiang2and Yang Chai1,* 1 The results indicated that AURKA-related proteins are involved in the processes of mitosis, cell cycle progression and apoptosis. Furthermore, these proteins are directly or indirectly associated with key molecules in crucial signaling pathways such as the Hippo pathway, the p53 pathway, the PI3K-Akt pathway, the FOXO pathway and the Wnt pathway Aurora kinase A (AURKA) is an essential cell cycle kinase involved in the mitotic phase of the cell cycle. AURKA is critical for proper completion of cell cycle progression . Its role in mitotic progression has been extensively characterised, and evidence for new AURKA functions emerges
The aurora kinase A inhibited by MLN 8054 are both implicated in cell cycle progression and, thus, in cellular proliferation.Epigenetic regulators were targeted by SAHA inhibiting HDACs and by DZNep inhibiting the histone methyltransferase EZH2, which silences genes by trimethylating histone H3K27.Combinations of small molecular inhibitors act synergistically in rhabdoid tumo The protein encoded by this gene is a cell cycle-regulated kinase that appears to be involved in microtubule formation and/or stabilization at the spindle pole during chromosome segregation. The encoded protein is found at the centrosome in interphase cells and at the spindle poles in mitosis Consistent with normally elevated expression during the G2 and M phases of the cell cycle, AURKA has been implicated as a key regulator of mitotic chromosome segregation through its functions in chromosome condensation, mitotic spindle assembly and the bipolar attachment of kinetochores to spindle microtubules, as well as entry into and exit from mitosis (4-9)
Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression (PubMed:26246606, PubMed:12390251, PubMed:18615013, PubMed:11039908, PubMed:17125279, PubMed:17360485). Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication. Aurora kinase A (AURKA) has been implicated in the regulation of cell cycle progression, mitosis and a key number of oncogenic signaling pathways in various malignancies including neuroblastoma. Small molecule inhibitors of AURKA have shown potential, but still not as good as expected effects in clinical trials. Little is known about this underlying mechanism
AURKA, a cell cycle-regulated kinase, is associated with malignant transformation and progression in many cancer types. We analyzed the expression change of AURKA in pan-cancer and its effect on the prognosis of cancer patients using the TCGA dataset AURKA is a serine-threonine kinase which is necessary for centrosome maturation and mitotic cell cycle progression. CDKN1A/p21 inhibits the activity of cyclin-dependent kinases CDK1, CDK2 and CDK4/6 complexes, so cyclin and cyclin-dependent kinase complexes are no longer functional, leading to inhibition of cell cycle progression Arid1a regulates cell cycle exit of transit-amplifying cells by inhibiting the Aurka-Cdk1 axis in mouse incisor In collection: Stem cells & regeneration Jiahui Du, Jiahui Du 1. Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, 90033, USA. 2. Although MYC or TAL1 depletion affected cell-cycle progression to some extent (Figures S3A and S3B), the corresponding changes in AURKB expression should not be a consequence of cell-cycle arrest as treatment of the CDK4/6 inhibitor Palbociclib (Palbo) induced G1 arrest but failed to change the AURKB expression (Figures S3C and S3D)
AURKA was strongly over-expressed in both A2058 and A375 cells in all cell cycle phases compared to empty vector (EV) control cells (Supplementary Fig. S1A). Phosphorylation of AURKA Thr288. In vitro, AURKA knockdown significantly reduced the viability of HuH-6 cells, while ALS treatment significantly suppressed HuH-6 cell proliferation and induced G1-phase cell cycle arrest by reducing cyclin-D1 expression. Moreover, ALS promoted apoptosis and autophagy by decreasing the activity of p38 MAPK in HuH-6 cells Aurora kinase A (AURKA) is a member of an evolutionary conserved family of serine/threonine protein kinases that plays essential roles in mitosis and meiosis. 1 Mammals possess 3 Aurora kinases: Aurora A, B, and C. AURKA functions at multiple stages of mitosis and is required for centrosome maturation, mitotic spindle formation, and accurate chromosome segregation AURKA plays a key role in regulating mitosis, and the activity of AURKA significantly increases during transition from the G2 to the M phase of the cell cycle . In addition, it has been reported that AURKA is closely related to the occurrence and development of various malignancies, such as endometrial cancer, colorectal adenocarcinoma and oral.
Aurka is known as a key cell-cycle regulator, whose levels of mRNA and protein are low in G1 and S and increase sharply during available under aCC-BY-NC-ND 4.0 International license. (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is mad AURKA undergoes targeted proteolysis in every cell cycle as a substrate of the Anaphase-Promoting Complex (APC/C) ubiquitin ligase at mitotic exit 18,19. However, AURKA is detectable in interphase cells and has been attributed a number of non-mitotic roles including ciliation control, cell cycle regulation of MYCN In somatic cells, both AURKA protein and kinase activity are low or undetectable through much of the cell cycle but rise sharply in G2 phase, most prominently on the duplicated centrosomes and then on the bipolar spindle in mitosis. pT288 staining is almost entirely confined to the centrosomes, in line with the idea that autophosphorylation is. Cell cycle progression is dependent, in part, on the activity of Aurora A kinase (AURKA) and protein phosphatase 1 (PP1) . PP1 regulates a myriad of cellular processes some tied to centrosome biology including mitosis, cytokinesis, and the cell cycle [10,11,12] . Protein interaction network analysis of screen hits revealed AURKA-centered interactions spanning the cell cycle, spliceosome, and tumor suppressors (Figure 5A )
in cell cycle regulation. The vertebrate Aurora family is composed of three members: Aurora-A (AURKA), Aurora-B (AURKB) and Aurora-C (AURKC),1 each of which exhibits a distinct sub-cellular localization and function during the cell cycle.2,3 AURKA was first isolated as a breast tumor amplified kinase,4 is frequently overex The acquisition of AurKa Pharma expands our pipeline with a promising oncology compound targeting a distinct cell cycle pathway. The work done by AurKa will allow Lilly to leverage emerging data about cancers in which this molecule might be effective, and determine if it can be beneficial to people living with various forms of cancer We investigated the role of Aurora kinase A (AURKA) in regulating p73-dependent apoptosis using the p53-deficient cancer cell lines H1299, TE7, and HCT116p53−/−. Overexpression of AURKA led to down-regulation of the TAp73-induced activation of the p53/p73-dependent luciferase reporter plasmid (pG13-luc). The reduction in the TAp73 transcription activity was confirmed by measuring the. Biotinylation of the centrosome and microtubules by V5-BirA*-AURKA in different cell cycle stages. After 18-h biotin incubation, HEK293T::V5-BirA*-AURKA were fixed and stained for the fusion protein with V5 antibody, biotinylated proteins with the fluorescent streptavidin, and the centrosome with gamma-tubulin antibody. DNA was stained with DAPI
AURKA sets in centrosomes in the early S phase and during mitosis an AURKA fraction correlates with spindle microtubules proximal to the spindle poles . AURKA has a role in cytokinesis and is activated by phosphorylation during G2/M phase transition in the cell cycle. Impaired AURKA may incline aneuploidy characteristics of tumors [3, 18] AURKA (aurora kinase A) is a centrosome-associated serine/threonine kinase which is associated with cell cycle checkpoint. It exhibits an inductive effect on the centrosome duplication-distribution abnormalities and aneuploidy in mammalian cells The Aurora kinases, which include Aurora A (AURKA), Aurora B (AURKB) and Aurora C (AURKC), are serine/threonine kinases required for the control of mitosis (AURKA and AURKB) and meiosis (AURKC). Since their discovery nearly 20 years ago, Aurora kinases have been studied extensively in cell and cancer biology
Aurora kinase A (AURKA) is a member of serine/threonine kinase family. Several kinases belonging to this family are activated in the G2/M phase of the cell cycle being involved in mitotic chromosomal segregation. AURKA overexpression is significantly associated with neoplastic transformation in several tumors and deregulated Aurora Kinases expression leads to chromosome instability, thus. Cell cycle and Northern blot analyses showed that peak expression of AURKA occurs during the G2/M phase and then decreases. Mapping By fluorescence in situ hybridization, Kimura et al. (1997) showed that the AURKA gene is represented by 2 signals in chromosome bands 20q13.2-q13.3 and 1q41-q42 Aurora kinase A (AURKA) is a therapeutic target in acute megakaryocytic leukemia. However, its requirement in normal hematopoiesis and megakaryocyte development has not been extensively characterized. Based on its role as a cell cycle regulator, we predicted that an Aurka deficiency would lead to severe abnormalities in all hematopoietic lineages Cell cycle (Georgetown, Tex.), 18(18), 2228-2238 (2019-07-31) Aurora-A is a serine/threonine kinase, which is overexpressed in multiple human cancers and plays a key role in tumorigenesis and tumor development
AURKA is overexpressed, both at the transcriptional and translational level. It is one of the three serine/threonine kinases that regulate chromosome separation and alignment during the cell cycle . In addition, AURKA also helps with the formation of the mitotic spindle fiber and activation of key signaling pathways  terations such as ampliﬁcation of the 20q13 region (AURKA locus) (Koynova et al., 2007). AURKA encodes Aurora kinase A, which is a serine/threonine kinase involved in mitotic spindle formation, centrosome separation, and G2/M phase transition during the cell cycle (D'Assoro et al. 2016). Increased AURKA expression has been reported from nevi t The cell cycle-related genes AURKA and FOXM1 are overexpressed in melanoma. We show here that AURKA overexpression is associated with poor prognosis in three independent cohorts of melanoma patients and correlates with the presence of genomic amplification of AURKA locus and BRAFV600E mutation. AURKA overexpression may also be driven by increased promoter activation through elements such as. The cell cycle is an important cellular process whereby the cell attempts to replicate its genome in an error-free manner. As such, mechanisms must exist for the cell cycle to respond to stress signals such as those elicited by hypoxia or reduced oxygen availability. This review focuses on the role of transcriptional and post-transcriptional mechanisms initiated in hypoxia that interface with. Aurora A protein levels are low during G1 and S phases and peak during the G2/M phase of the cell cycle. Phosphorylation of Aurora A at Thr288 in its catalytic domain increases kinase activity. Aurora A is involved in centrosome separation, maturation, and spindle assembly and stability. Expression of Aurora B protein also peaks during the G2/M.
Aurora kinase A (AURKA) is a putative low-penetrance tumor susceptibility gene in cell cycle regulation and centrosomal function , which is essential for centrosome function and maturation, spindle assembly, chromosome alignment, and mitotic entry . In addition, YBX1 promotes AURKA protein expression by directly binding to its mRNA. Loss of YBX1 leads to reduction of AURKA protein level. Forced expression of AURKA rescues cell proliferation and invasiveness in YBX1-silenced NPC cell
Aims To assess the expression of the following cell cycle regulatory proteins in primary metastatic breast carcinomas (MBCs) and on availability in matched distant metastases (DMs): Ki67, cyclin A, geminin and aurora-kinase A (aurkA); and to compare the expression of these markers in early MBC (EMBC) and late MBC separated into groups according to median time point on metastatic event occurred. An Alternative Splicing Network Links Cell-Cycle Control to Apoptosis. Cell, 2010. Pamela Silver. Michael Moore. Q. Wang. Pamela Silver. Michael Moore. Q. Wang. Download PDF. Download Full PDF Package. This paper. A short summary of this paper. 37 Full PDFs related to this paper. READ PAPER This pool appears also to be involved in the non-mitotic role of AURKA in cilia disassembly at cell cycle reentry from G0 (92, 96), a process that also requires Plk1 activity . An additional interactor of AURKA involved in both cell-cell adhesion and cell proliferation and survival ( 97 ) is Ajuba leukemia cell lines with somatic mutations, and that KDM6B up-regulates the cell cycle inhibitor p21, resulting in cell cy cle arrest (van Haaften et al., 2009; Zhao et al., 2013). In this study, we investigated the role of AURKA-mediated leukemia cell differentiation via the modulation of KDM6B expression in MLL-AF9 AML cells. We demonstrated tha
When the AURKA levels go back up, then the cell can divide, and the cancer can continue growing. Yale Cancer Center scientists now propose that if you give the two inhibitors together, WEE1 inhibition can remove the brakes on cell cycle arrest, so that the cell goes ahead and divides despite the damage AURKA inflicts, and the cell dies CiteSeerX - Document Details (Isaac Councill, Lee Giles, Pradeep Teregowda): Aurora kinase A (AURKA), a serine/threonine kinase, has been shown to regulate the cell cycle checkpoint and maintain genomic integrity. AURKA is overexpressed in various carcinomas. Breast cancer 2, early onset (BRCA2) has an important role in maintaining genomic stability and acts as a tumor suppressor Impact on stem cell properties was evaluated by flow cytometry analysis of surface markers and sphere formation assays. Gene expression analyses followed by functional annotation identified a series of deregulated genes that belonged to cell cycle, including AURKA/B, TTK kinase, and CHEK1
Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and. AURKA and WEE1 play major roles in the cell cycle, in which the cell creates two complete sets of DNA and then divides into two. In one phase of this cycle, the dividing cell creates spindles. From the start codon through the stop codon, the length of the fully processed AURKA mRNA is 1,212 nucleotides. Calculate the number of amino acids in the polypeptide chain coded for by the mRNA. 3. Predict the effect of a mutation that prevents the expression of AURKA on a normal (noncancerous) cell. 4
Jong Woo Lee, PhD is an Associate Research Scientist at the Yale Cancer Center and Yale University School of Medicine. He has expertise on numerous innovative techniques covering cancer biology, pharmacology, metabolism and in vivo preclinical evaluation of therapeutics including targeted therapy and immuno-oncology. His research has mainly been focusing on translational cancer research by. The Ecdysone receptor constrains wingless expression to pattern cell cycle across the Drosophila wing margin in a cyclin B-dependent manner. BMC Dev Biol 13: 28. PubMed ID: 23848468 Quinn, L. M., Secombe, J. and Hime, G. R. (2013). Myc in stem cell behaviour: insights from Drosophila. Adv Exp Med Biol 786: 269-285. PubMed ID: 2369636 AURKA (Aurora Kinase A) belongs to the mitotic serine/threonine kinases family. AURKA is a cell cycle-regulated kinase which may be involved in microtubule formation and/or stabilization at the spindle pole during chromosome segregation. AURKA is found at the centrosome in interphase cells and at the spindle poles in mitosis Aurora kinase A (AURKA) is a crucial member of the Aurora/Ipl1p kinase family, acting as a cell-cycle associated kinase on maintaining genomic integrity [8, 9]. To ensure the successful completion of mitosis, AURKA is involved in separation and maturation of the central body, as well as stabilization at the spindle pole during chromosome. Cell Cycle Inhibitors: AURKA/B Treatment given for recurrence occurring at any time after last platinum-based treatment. Objective Response Rate (%) Percentage of patients whose tumors shrink or go away after treatment. Progression Free Survival (months
.2; C13orf34) complex formation [29, 38, 43, 57]. A mechanism was suggested recently, according to which BORA and AURKA together control transition from phase G2 of cell cycle to phase M . According to the proposed mechanism, Cdk1 causes BORA to exit from the. aurora kinase a (aurKa) regulates the cell cycle checkpoint and maintains genomic integrity. aurKa is overexpressed in various malignant tumors and its upregulation induces chromosomal instability, which leads to aneuploidy and cell transformation. to investigate the role of aurKa in endometrial cancer, we evaluated the association of immunohistochemical expression of aurKa with. Introduction. AURKA is a serine/threonine kinase with multiple functions during interphase and cell division. It is frequently overexpressed in solid tumours and during haematological malignancies, where it correlates with poor patient survival and resistance to treatments (Farag, 2011; Nikonova et al, 2013; Bertolin & Tramier, 2020).AURKA was originally found at centrosomes and at the mitotic.
tion of the Aurora kinases during the cell cycle, leading to their distinct cellular functions 6-9. In particular, AURKA has been implicated in multiple events accompanying transit through the G2 to M phases of the cell cycle, and during mitotic cell division. These include centrosome multiplication 10,11 and matura To identify drugs synthetic lethal with RB1 mutation ( RB1 mut), we tested 36 cell-cycle inhibitors using a cancer cell panel profiling approach optimized to discern cytotoxic from cytostatic effects. Inhibitors of the Aurora kinases AURKA and AURKB showed the strongest RB1 association in this assay the cell cycle . In addition, AURKA also helps with the formation of the mitotic spindle fiber and activation of key signaling pathways . In gastric cancer, AURKA overexpression leads to increased expression and phosphory-lation of Human Doubling Minute 2 (HDM2), coupled with suppression of p53 and its downstream targets Due to the crucial role of AURKA in mitosis, the cell cycle blocking effect on NB4 and HL-60 cells was examined. PW21 greatly induced G 2 /M cell cycle arrest and polyploidization in AML cells (Figure 4C). An immunofluorescence assay further confirmed that PW21 induced polyploidy in cells (Figure 4D) Journal of Bone Oncology (2019-12-01) . A screening-based approach identifies cell cycle regulators AURKA, CHK1 and PLK1 as targetable regulators of chondrosarcoma cell surviva
Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and. Myc oncoproteins promote continuous cell growth, in part by controlling the transcription of key cell cycle regulators. Here, we report that c-Myc regulates the expression of Aurora A and B kinases (Aurka and Aurkb), and that Aurka and Aurkb transcripts and protein levels are highly elevated in Myc-driven B-cell lymphomas in both mice and humans.The induction of Aurka by Myc is transcriptional.
All risk genes for prognosis of HGA including CDC6 (cell division cycle 6), AURKA (aurora kinase A) and CHEK1 (checkpoint kinase 1) were significantly enriched in cell cycle, mitotic as well as mitotic anaphase. While the genes in the network module such as CDC6, AURKA and CHEK1 mainly participated in functions such as cell cycle, mitotic cell. Mammalian cells have three types of Aurora kinases, AURKA, AURKB, and AURKC which have specific subcellular localizations and functions during cell cycle 14, 15. Aurora kinase A (AURKA) is a well-known oncogene and serin/threonin kinase 16, which is localized at the centrosome from the moment of centrosome duplication to mitotic completion, and. AURKA and AURKB is regulated in a cell cycle-dependent manner. The promoter regions of these genes contain a cell cycle-dependent element (CDE) and a cell cycle gene homology region (CHR), where transcription factors E2F1, E2F4, and DP2 bind [18, 19]. The oncoprotein c-Myc has been found to dir-ectly activate the transcription of AURKA via E-boxe Cell cycle progression is dependent, in part, on the ac-tivity of Aurora A kinase (AURKA) and protein phos-phatase 1 (PP1) . PP1 regulates a myriad of cellular processes some tied to centrosome biology including mi-tosis, cytokinesis, and the cell cycle [10-12]. PP1's roles are specified by binding of its catalytic subunit to a
Subject Categories Cell Adhesion, Polarity & Cytoskeleton; Cell Cycle DOI 10.15252/embr.202051902|Received 19 October 2020|Revised 19 May 2021|Accepted 26 May 2021 EMBO Reports (2021)e51902 Introduction Aurora kinase A (AURKA) is a member of the evolutionarily conserved Aurora serine/threonine kinase family and a pleiotropi cell cycle events. Mammalian oocytes express all three Aurk isoforms throughout AurkA siRNA speciﬁcity was determined on both AurkA transcriptional and translational levels in germinal vesicle-intact (GVI) oocytes just before re-initiation of meiosis wit MLN8237 is the first orally available small molecule inhibitor of AURKA with a half maximal inhibitory concentration (IC50) value of 1.2 nM, as measured by enzymatic assays. 31 Cell-based assays showed that MLN8237 is at least 200-fold more selective for AURKA (IC50, 6.7 nM) than AURKB (IC50, 1534 nM). 31 Exposure of imatinib-resistant Ba/F3. cell.2,4,19,31 AURKA localizes next to the centrosome late in the G 1 phase and early in the S phase. It plays a crucial role in the G 2/M checkpoint of cell cycle to undergo mitosis and meiosis. It is activated by one or more phosphorylations and its activity peaks during the G 2/M transition in the cell cycle. In addition to spindl serine/threonine protein kinase which is regulated by the cell cycle; may be involved in microtubule formation and/or stabilization at the spindle pole during chomosome segregation [RGD, Feb 2006] Select a product type
As a serine/threonine kinases, AURKA activity peaks during the G2/M phase transition phase in the cell cycle, and associated with the regulation of spindle stability. Aurora A dysregulation has been associated with high occurrence of various cancers, for example breast, prostate, bladder, colorectal, gastric, ovarian, esophagus and pancreatic. Description AURKA Human is a single, non-glycosylated, polypeptide chain containing 423 amino acids (1-403). AURKA is fused to 20 a.a. His-Tag at N-terminus and purified by proprietary chromatographic techniques. AURKA.. Aurora kinase A (AURKA), a serine/threonine kinase that plays a critical role in regulating cell cycle and mitosis in normal cells, is frequently amplified and/or overexpressed in GI malignancies (including esophageal, gastric, and colorectal cancers [CRCs]) Furthermore, the down-regulation of AurkA expression may inhibit proliferation and cell cycle exit, which favors differentiation. Upon correlating these observations in the context of Aurora kinase-mediated phosphorylation, we found that blocking the kinase activity of AurkA alone induced nuclear retention and was detrimental to skeletal.