A5042916490- Drug Transport and Resistance Mechanisms
- RNA Research and Splicing
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Melanoma and MAPK Pathways
- Cancer Treatment and Pharmacology
- Cancer therapeutics and mechanisms
- Genomics and Chromatin Dynamics
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer Mechanisms and Therapy
- DNA Repair Mechanisms
- Cell death mechanisms and regulation
- MicroRNA in disease regulation
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Synthesis and biological activity
- RNA and protein synthesis mechanisms
- Chemical Synthesis and Analysis
- Synthesis and Catalytic Reactions
- Protein Degradation and Inhibitors
- Immunotherapy and Immune Responses
- Mycobacterium research and diagnosis
- Cancer Genomics and Diagnostics
- FOXO transcription factor regulation
University of Würzburg
2016-2024
Fondazione IRCCS Istituto Nazionale dei Tumori
2009-2016
University of Milan
2009-2012
Deregulated expression of MYC induces a dependence on the NUAK1 kinase, but molecular mechanisms underlying this have not been fully clarified. Here, we show that is predominantly nuclear protein associates with network phosphatase 1 (PP1) interactors and PNUTS, regulatory subunit PP1, phosphorylated by NUAK1. Both PNUTS associate splicing machinery. Inhibition abolishes chromatin association reduces spliceosome activity, suppresses nascent RNA synthesis. Activation does bypass requirement...
Abstract RNA-binding proteins emerge as effectors of the DNA damage response (DDR). The multifunctional non-POU domain-containing octamer-binding protein NONO/p54nrb marks nuclear paraspeckles in unperturbed cells, but also undergoes re-localization to nucleolus upon induction double-strand breaks (DSBs). However, NONO nucleolar is poorly understood. Here we show that topoisomerase II inhibitor etoposide stimulates production RNA polymerase II-dependent, damage-inducible antisense intergenic...
Abstract In pancreatic ductal adenocarcinoma (PDAC), endogenous MYC is required for S-phase progression and escape from immune surveillance. Here we show that in PDAC cells needed the recruitment of PAF1c transcription elongation complex to RNA polymerase depletion CTR9, a subunit, enables long-term survival PDAC-bearing mice. largely dispensable normal proliferation regulation target genes. Instead, limits DNA damage associated with by being essential expression long genes involved...
Mitogen-activated protein kinases (MAPK) are involved in a complex network which regulates variety of cellular processes including proliferation, survival and death. The molecular characterization the pathway has shown aberrant activation several human tumors, due to deregulation receptor tyrosine or mutations components. Progress understanding MAPK led development target-specific agents clinical trials. relevance response resistance antitumor been recognized, although outcome can vary...
The MYCN oncoprotein binds active promoters in a heterodimer with its partner protein MAX. also interacts the nuclear exosome, 3′-5′ exoribonuclease complex, suggesting function RNA metabolism. Here, we show that forms stable high-molecular-weight complexes exosome and multiple RNA-binding proteins. vitro cells via conserved sequence termed MYCBoxI. In cells, associates thousands of intronic transcripts together ZCCHC8 subunit targeting complex enhances their processing. Perturbing results...
Since response to platinum-based therapy in non–small-cell lung cancer (NSCLC) is poor, the present study was designed rationally identify novel drug combinations cell models including A549 line and cisplatin-resistant subline A549/Pt, characterized by reduced sensitivity cisplatin-induced apoptosis upregulation of efflux transporters ATP binding cassette (ABC) superfamily. Given molecular features these cells, we focused on compounds triggering through different mechanisms, such as...
(Molecular Cell 77, 1322–1339.e1–e11; March 19, 2020) After discussion among the co-authors, who are all in agreement, Amit Kumar’s contribution to this paper warranted inclusion as a co-author. The authors regret omission. has since been corrected online, including author list, acknowledgments, and contributions, which also appear here. We acknowledge Andreas Schlosser at mass spectrometry technology platform Rudolf-Virchow-Zentrum, Würzburg, for FLAG-NUAK1 label-free proteomic experiments....
ABSTRACT RNA-binding proteins (RBPs) stimulate the DNA damage response (DDR). The RBP NONO marks nuclear paraspeckles in unperturbed cells and undergoes poorly understood re-localisation to nucleolus upon induction of double-strand breaks (DSBs). Here we show that treatment with topoisomerase-II inhibitor etoposide stimulates production RNA polymerase II-dependent, damage-induced nucleolar antisense RNAs (diNARs) human cells. diNARs originate from intergenic spacer tether via its RRM1...
Mitogen-activated protein kinases (MAPK) are involved in a complex network which regulates variety of cellular processes including proliferation, survival and death. The molecular characterization the pathway has shown aberrant activation several human tumors, due to deregulation receptor tyrosine or mutations components. Progress understanding MAPK led development target-specific agents clinical trials. relevance response resistance antitumor been recognized, although outcome can vary...