A5077626637- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- RNA modifications and cancer
- Cellular transport and secretion
- Fungal and yeast genetics research
- Cancer-related gene regulation
- DNA Repair Mechanisms
- Cell death mechanisms and regulation
- RNA Research and Splicing
- Cancer Research and Treatments
- Mitochondrial Function and Pathology
- Protein Kinase Regulation and GTPase Signaling
- Lymphoma Diagnosis and Treatment
- Erythropoietin and Anemia Treatment
- RNA and protein synthesis mechanisms
- Cancer, Hypoxia, and Metabolism
- Erythrocyte Function and Pathophysiology
- Blood Coagulation and Thrombosis Mechanisms
- Plant Reproductive Biology
- MicroRNA in disease regulation
- Genomics and Chromatin Dynamics
- Endoplasmic Reticulum Stress and Disease
- Acute Myeloid Leukemia Research
Innsbruck Medical University
2013-2024
Universität Innsbruck
2006-2024
University of Oslo
2012
Max Planck Institute of Biochemistry
1998-2007
Max Planck Society
1990-2006
Sunnybrook Health Science Centre
2003
University of North Carolina at Chapel Hill
2003
Scripps Research Institute
1994-1998
Washington University in St. Louis
1996
Max Planck Institute for Biophysical Chemistry
1990-1994
Cell cycle phase transitions in eukaryotic cells are driven by regulation of the activity protein kinases known as cyclin-dependent (Cdks). A broad spectrum Cdk-inhibitory associated with a 28-kilodalton (p28 Ick1 ) was induced treated drug lovastatin or upon density-mediated growth arrest and periodic cell cycle, peak G 1 . The p28 shown to be identical p27 Kip1 , inhibitory resulted from accumulation protein. Variations amount occurred, whereas abundance messenger RNA remained unchanged....
It has been proposed that the functions of cyclin-dependent kinase inhibitors p21Cip1/Waf1 and p27Kip1 are limited to cell cycle control at G1/S-phase transition in maintenance cellular quiescence. To test validity this hypothesis, p21 was expressed a diverse panel lines, thus isolating effects activity from pleiotropic upstream signaling pathways normally induce expression. The data show physiological levels accumulation, p21, addition its role negatively regulating G1/S transition,...
The cyclin-dependent kinase (Cdk) inhibitor p21Waf1/Cip1/Sdi1, important for p53-dependent cell cycle control, mediates G1/S arrest through inhibition of Cdks and possibly DNA replication. Cdk requires a sequence approximately 60 amino acids within the p21 NH2 terminus. We show, using proteolytic mapping, circular dichroism spectropolarimetry, nuclear magnetic resonance spectroscopy, that NH2-terminal fragments are active as inhibitors lack stable secondary or tertiary structure in free...
Transforming growth factor beta (TGF-beta) is a potent inhibitor of epithelial cell growth. Cyclins E and A in association with Cdk2 have been shown to play role the G1-to-S phase transition mammalian cells. We studied effects TGF-beta-mediated arrest on G1/S cyclins A. Inhibition cyclin A-associated kinase by TGF-beta primarily due decrease mRNA protein. By contrast, while inhibits accumulation mRNA, reduction protein minimal. Instead, we find that activation E-associated normally...
p27 Kip1 restrains cell proliferation by binding to and inhibiting cyclin-dependent kinases. To investigate the mechanisms of translational regulation, we isolated a complete cDNA identified an internal ribosomal entry site (IRES) located in its 5′UTR. The IRES allows for efficient translation under conditions where cap-dependent is reduced. Searching possible regulators activity have neuronal ELAV protein HuD as specific factor Increased expression or ubiquitously expressed HuR specifically...
Cyclin-dependent kinases (Cdks) previously have been shown to drive the major cell cycle transitions in eukaryotic organisms ranging from yeast humans. We report here identification of a 28-kDa protein, p28Ick (inhibitor cyclin-dependent kinase), that binds and inhibits kinase activity preformed Cdk/cyclin complexes human cells. p28 inhibitory fluctuates during with maximal levels G1 accumulates G1- G0-arrested These results suggest control G1/S transition may be influenced by family Cdk...
AbstractWe have created fibroblast cell lines that express cyclin A under the control of a tetracycline-repressible promoter. When stimulated to reenter cycle after serum withdrawal, these cells were advanced prematurely into S phase by induction A. In an asynchronous population, caused decrease in percentage G1. These results demonstrate expression is rate limiting for G1-to-S transition and suggest can function as G1 cyclin. Although level exogenous was constant throughout cycle, its...
We show that p27 localization is cell cycle regulated and we suggest active CRM1/RanGTP-mediated nuclear export of may be linked to cytoplasmic proteolysis in early G1. G0 G1 appears transiently the cytoplasm at G1/S transition. Association with exportin CRM1 was minimal increased markedly during G1-to-S phase progression. Proteasome inhibition mid-G1 did not impair import p27, but led accumulation cytoplasm, suggesting precedes degradation for least part cellular pool. p27-CRM1 binding were...
Prostate cancer development and progression are associated with alterations in expression function of elements cytokine networks, some which can activate multiple signaling pathways. Protein inhibitor activated signal transducers activators transcription (PIAS)1, a regulator signaling, may be implicated the modulation cellular events during carcinogenesis. This study was designed to investigate functional significance PIAS1 models human prostate cancer. We demonstrate for first time that...
Abundance and activity of the tumor suppressor p53 are regulated by many different posttranslational modifications. These include phosphorylation, acetylation, ribosylation, O-glycosylation or ubiquitination. Three years ago, covalent modification with ubiquitin- related protein SUMO-1 has been added to this list. resembles ubiquitin both in structure mechanism attachment, is reversibly attached a large number proteins. Molecular consequences dynamic vary between targets alterations...
Cell-cycle phase transitions are controlled by cyclin-dependent kinases (Cdks). Key to the regulation of these kinase activities Cdk inhibitors, proteins that induced in response various antiproliferative signals but can also oscillate during cell-cycle progression, leading inactivation. A current dogma is complexes containing prototype inhibitor p21 transit between active and inactive states, associated with one molecule remain until they associate additional molecules. However, using a...
A clone designated A.t.RAB6 encoding a small GTP-binding protein was isolated from cDNA library of Arabidopsis thaliana leaf tissue. The predicted amino acid sequence highly homologous to the mammalian and yeast counterparts, H.Rab6 Ryh1/Ypt6, respectively. Lesser homology found between two proteins plant species (44% Zea mays Ypt1 43% Nicotiana tabacum Rab5). Conserved stretches in deduced A.t.Rab6 include four regions involved GTP-binding, an effector region, C-terminal cysteine residues...
Cell cycle progression, including genome duplication, is orchestrated by cyclin-dependent kinases (CDKs). CDK activation depends on phosphorylation of their T-loop a CDK–activating kinase (CAK). In animals, the only known CAK for CDK2 and CDK1 cyclin H-CDK7, which constitutively active. Therefore, critical step dephosphorylation inhibitory sites Cdc25 phosphatases rather than unrestricted phosphorylation. Homologous CDK4 CDK6 bound to cyclins D are master integrators mitogenic/oncogenic...