A5060572157- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- Ovarian cancer diagnosis and treatment
- 14-3-3 protein interactions
- Cancer, Hypoxia, and Metabolism
- Photosynthetic Processes and Mechanisms
- Cellular transport and secretion
- Cancer, Lipids, and Metabolism
- Metabolism, Diabetes, and Cancer
- Cell death mechanisms and regulation
- Cancer Mechanisms and Therapy
- Nuclear Structure and Function
- Caveolin-1 and cellular processes
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Cancer Research and Treatments
- Nanoparticle-Based Drug Delivery
- Genetic factors in colorectal cancer
- Epigenetics and DNA Methylation
- Endometrial and Cervical Cancer Treatments
- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
Goethe University Frankfurt
2014-2024
University Hospital Frankfurt
2013-2023
Friedrich Schiller University Jena
2019
Jena University Hospital
2014-2019
Goethe Institute
2013-2015
Indiana University School of Medicine
2013
Bielefeld University
2010
German Cancer Research Center
2010
Heidelberg University
2010
Caspase activation is a hallmark of apoptosis. However, the molecular mechanisms underlying regulation caspase-8 within extrinsic death pathway are not well understood. In this study, we demonstrate that procaspase-8 phosphorylated in mitotic cells by Cdk1/cyclin B1 on Ser-387, which located at N terminus catalytic subunit p10. This phosphorylation Ser-387 occurs cancer cell lines, as primary breast tissues and lymphocytes. Furthermore, RNA interference-mediated silencing cyclin or treatment...
High attrition rates of novel anti-cancer drugs highlight the need for improved models to predict toxicity. Although polo-like kinase 1 (Plk1) inhibitors are attractive candidates drug development, role Plk1 in primary cells remains widely unexplored. Therefore, we evaluated utility an RNA interference-based model assess responses inducible knockdown (iKD) adult mice. Here show that silencing can be achieved several organs, although adverse events rare. We compared Plk1-iKD mice with those...
The spindle assembly checkpoint (SAC) acts as a molecular safeguard in ensuring faithful chromosome transmission during mitosis, which is regulated by complex interplay between phosphatases and kinases including PLK1. Adenomatous polyposis coli (APC) germline mutations cause aneuploidy are responsible for familial adenomatous (FAP). Here we study the role of PLK1 colon cancer cells with chromosomal instability promoted APC truncation (APC-ΔC). expression APC-ΔC reduces accumulation mitotic...
Exposure to drugs that interfere with microtubule dynamics block cell cycle progression at mitosis by prolonged activation of the spindle assembly checkpoint (SAC). Cells can evade mitotic arrest and proceed interphase without chromosome segregation a process termed slippage involves Cyclin B1 degradation inactivation. Here, we explored cellular response small-molecule inhibitors Polo-like kinase 1 (Plk1), an important regulator division. We found clinical Plk1 BI 2536 6727, both...
Salt-inducible kinases (SIKs) are key metabolic regulators. The imbalance in SIK function is associated with the development of diverse cancers, including breast, gastric, and ovarian cancers. Chemical tools to clarify roles different diseases are, however, sparse generally characterized by poor kinome-wide selectivity. Here, we have adapted pyrido[2,3-d]pyrimidin-7-one-based p21-activated kinase (PAK) inhibitor G-5555 for targeting SIK, exploiting differences back-pocket region these...
Mitotic centromere-associated kinesin (MCAK) plays an essential role in spindle formation and correction of improper microtubule-kinetochore attachments. The localization activity MCAK at the centromere/kinetochore are controlled by Aurora B kinase. However, is also abundant cytosol centrosomes during mitosis, its regulatory mechanism these sites unknown. We show here that cyclin-dependent kinase 1 (Cdk1) phosphorylates T537 core domain attenuates microtubule-destabilizing vitro vivo....
Abstract Background The cellular tumor protein p53 ( TP53 ) is a suppressor gene that frequently mutated in human cancers. Among various cancer types, the very aggressive high‐grade serous ovarian carcinoma (HGSOC) exhibits highest prevalence of mutations, present >96% cases. Despite intensive efforts to reactivate p53, no clinical drug has been approved rescue function. In this study, our primary objective was administer vitro‐transcribed (IVT) wild‐type (WT) p53‐mRNA HGSOC cell lines,...
Polo-like kinase 1 (Plk1) is overexpressed in tumor tissues and its expression level tightly associated with the malignancy of tumors prognosis patients. Thus, Plk1 considered as one most attractive molecular targets for anticancer therapy. Recently, several small molecule inhibitors have been identified characterized, first generation has investigated clinical trials. However, long-term effect downregulation on cells not yet studied. In this work we phenotype HeLa cells, which continuously...
// Mourad Sanhaji 1* , Andreas Ritter 1 Hannah R. Belsham 2 Claire T. Friel Susanne Roth Frank Louwen and Juping Yuan Department of Gynecology Obstetrics, School Medicine, J. W. Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany. Life Sciences, University Nottingham, Medical School, Queen’s Centre, NG7 2UH, United Kingdom. * Present address: Hospital Jena, Institute for Diagnostic Interventional Radiology, Experimental Erlanger Allee 101, 07747 Germany Correspondence:...
Upon interaction of the CD95 receptor with its ligand, sequential association adaptor molecule FADD (MORT1), pro-forms caspases-8/10, and caspase-8/10 regulator c-FLIP leads to formation a death-inducing signaling complex. Here, we identify polo-like kinase (Plk) 3 as new partner death CD95. The enzymatic activity Plk3 increases following ligand. Knockout (KO) or knockdown caspase-8, prevents activation upon stimulation, suggesting requirement functional DISC for activation. Furthermore,...
Mitotic centromere-associated kinesin (MCAK) is the best characterized member of kinesin-13 family and plays important roles in microtubule dynamics during mitosis. Its activity subcellular localization tightly regulated by an orchestra mitotic kinases, such as Aurora B. It well known that serine 196 MCAK major phosphorylation site B Xenopus leavis extracts this regulates its catalytic localization. In current study, we have addressed conserved 192 human to characterize function more depth...
In this paper we show that conjugation of magnetic nanoparticles (MNPs) with Gemcitabine and/or NucAnt (N6L) fostered their internalization into pancreatic tumor cells and the coupling procedure did not alter cytotoxic potential drugs. By treating (BxPC3 PANC-1) conjugated MNPs hyperthermia (43 °C, 60 min), cell death was observed. The two lines showed different reactions against combined therapy according to intrinsic sensitivity (cell death, ROS production, ability activate ERK 1/2 JNK)....
Paclitaxel is a frontline drug for the treatment of epithelial ovarian cancer (EOC). However, following paclitaxel-platinum based chemotherapy, tumor recurrence occurs in most patients. Chromosomal instability (CIN) hallmark and represents genetic variation fueling adaptation to cytotoxic effects anticancer drugs. In this study, our Kaplan-Meier analysis including 263 patients (stages I/II) revealed that high Polo-like kinase (PLK) 1 expression correlates with bad prognosis. To evaluate role...
Polo-like kinase 1 (Plk1) is elementary for cell proliferation and its deregulation involved in tumorigenesis. Plk1 has been established as one of the most attractive targets molecular cancer therapy. In fact, multiple small molecule inhibitors targeting either domain or Polo-box binding (PBD) have identified intensively investigated. Intriguingly, depletion affects more cells than normal cells. It also reported that cytotoxicity induced by inhibition elevated with defective p53. The data...
Mitotic centromere-associated kinesin (MCAK) is an ATP-dependent microtubule (MT) depolymerase regulated by Aurora kinase (AURK) phosphorylation and implicated in resolution of improper MT attachments mitosis. Distribution MCAK was studied oocyte maturation anti-MCAK antibody, anti-tubulin anti-AURKB antibody anti-centromere (ACA) the expression MCAK-enhanced green fluorescent protein fusion maturing mouse oocytes. Function assessed knockdown Mad2, inhibiting AURK or proteasome, live imaging...
Polo-like kinase 1 has been established as one of the most attractive targets for molecular cancer therapy. In fact, multiple small-molecule inhibitors targeting this have developed and intensively investigated. Recently, it reported that cytotoxicity induced by Plk1 inhibition is elevated in cells with inactive p53, leading to hypothesis p53 a predictive marker response inhibition. our previous study based on different cell lines, we showed wild type were more sensitive inducing apoptosis,...
The taxanes are effective microtubule-stabilizing chemotherapy drugs that inhibit mitosis, induce apoptosis, and produce regression in a fraction of cancers arise at many sites including the ovary. Novel therapeutic targets augment taxane effects needed to improve clinical response CCNE1-amplified high grade serous ovarian cancer (HGSOC) cells. In this study, we conducted an siRNA-based kinome screen identify modulators mitotic progression HGSOC cells may influence paclitaxel response. PLK1...
Since type and duration of an appropriate adjuvant chemotherapy in early-stage ovarian cancer (OC) are still being debated, novel markers for a better stratification these patients utmost importance the design improved chemotherapeutical strategy. In contrast to numerous studies on cellular proliferation based immunohistochemistry-driven evaluation protein expression, we compared mRNA expression two independent proliferation, Ki-67 Plk1, large cohort 243 OC their relationship with...
The activity of the Salt inducible kinase 2 (SIK2), a member AMP-activated protein (AMPK)-related family, has been linked to several biological processes that maintain cellular and energetic homeostasis. SIK2 is overexpressed in cancers, including ovarian cancer, where it promotes proliferation metastases. Furthermore, as centrosome kinase, shown regulate G2/M transition, its depletion sensitizes cancer paclitaxel-based chemotherapy. Here, we report consequences inhibition on mitosis...