A5090826499- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Hedgehog Signaling Pathway Studies
- Wnt/β-catenin signaling in development and cancer
- DNA Repair Mechanisms
- Cancer-related gene regulation
- RNA modifications and cancer
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
- Genomics and Chromatin Dynamics
- Cell Adhesion Molecules Research
- Cellular transport and secretion
- interferon and immune responses
- Genetics and Neurodevelopmental Disorders
- Developmental Biology and Gene Regulation
- Glioma Diagnosis and Treatment
- Caveolin-1 and cellular processes
- Autophagy in Disease and Therapy
- NF-κB Signaling Pathways
- Chemokine receptors and signaling
- Renal and related cancers
- Histone Deacetylase Inhibitors Research
University of Verona
2018-2025
Hubrecht Institute for Developmental Biology and Stem Cell Research
2011-2020
University Medical Center Utrecht
2011-2020
Utrecht University
2010-2018
Royal Netherlands Academy of Arts and Sciences
2014
New York University
1999-2009
National Cancer Institute
2006
University of Virginia
2006
Howard Hughes Medical Institute
2002
Institute of Neurobiology and Molecular Medicine
1994-2000
The tumor suppressor programmed cell death protein 4 (PDCD4) inhibits the translation initiation factor eIF4A, an RNA helicase that catalyzes unwinding of secondary structure at 5' untranslated region (5'UTR) messenger RNAs (mRNAs). In response to mitogens, PDCD4 was rapidly phosphorylated on Ser67 by kinase S6K1 and subsequently degraded via ubiquitin ligase SCF(betaTRCP). Expression in cultured cells a stable mutant is unable bind betaTRCP inhibited mRNA with structured 5'UTR, resulted...
F-box proteins are an expanding family of eukaryotic characterized by approximately 40 aminoacid motif, the F box (so named because cyclin was one first in which this motif identified) [[1]Bai C Sen P Hofman K Ma L Goebel M Harper W Elledge S Skp1 connects cell cycle regulators to ubiquitin proteolysis machinery through a novel F-box.Cell. 1996; 86: 263-274Abstract Full Text PDF PubMed Scopus (932) Google Scholar]. Some have been shown be critical for controlled degradation cellular...
The p53-inducible gene PC3 (TIS21, BTG2) is endowed with antiproliferative activity. Here we report that expression of in cycling cells induced accumulation hypophosphorylated, growth-inhibitory forms pRb and led to G(1) arrest. This latter was not observed genetic disruption the Rb gene, indicating PC3-mediated arrest dependent. Furthermore, (i) G(1)-S transition exerted by completely rescued coexpression cyclin D1 but A or E; (ii) caused a significant down-regulation protein levels, also...
Persistent infection of basal keratinocytes with high-risk human papillomavirus (hrHPV) may cause cancer. Keratinocytes are equipped different pattern recognition receptors (PRRs) but hrHPV has developed ways to dampen their signals resulting in minimal inflammation and evasion host immunity for sustained periods time. To understand the mechanisms underlying hrHPV's capacity evade immunity, we studied PRR signaling non, newly, persistently hrHPV-infected keratinocytes. We found that active...
Rac1 regulates a wide variety of cellular processes. The polybasic region the C terminus functions both as plasma membrane–targeting motif and nuclear localization sequence (NLS). We show that triproline N-terminal to contributes NLS, which is cryptic in sense it strongly inhibited by geranylgeranylation adjacent cysteine. Subcellular fractionation demonstrated endogenous nucleus Triton X-114 partition revealed this pool prenylated. Cell cycle–blocking agents, synchronization cells stably...
We have applied a proteolysis targeting chimera (PROTAC) technology to obtain peptidomimetic molecule able trigger the degradation of SARS-CoV-2 3-chymotrypsin-like protease (3CLPro). The PROTAC was designed by conjugating GC-376 based dipeptidyl 3CLPro ligand pomalidomide moiety through piperazine–piperidine linker. NMR and crystallographic data complemented with enzymatic cellular studies showed that (i) binds active site dimeric state forming reversible covalent bond sulfur atom catalytic...
AbstractHeterochromatin plays an essential role in the preservation of epigenetic information, transcriptional repression repetitive DNA elements and inactive genes proper segregation chromosomes during mitosis. Here we identify KDM2A, a JmjC-domain containing histone demethylase, as heterochromatin-associated HP1-interacting protein that promotes HP1 localization to chromatin. We show KDM2A is required maintain heterochromatic state, determined using candidate-based approach coupled vivo...
The kinase eEF2K [eukaryotic elongation factor 2 (eEF2) kinase] controls the rate of peptide chain by phosphorylating eEF2, protein that mediates movement ribosome along mRNA promoting translocation transfer RNA from A to P site in ribosome. eEF2K-mediated phosphorylation eEF2 on threonine 56 (Thr⁵⁶) decreases its affinity for ribosome, thereby inhibiting elongation. Here, we show response genotoxic stress, was activated AMPK (adenosine monophosphate-activated kinase)-mediated serine 398....
Suppressor of Fused (SuFu), a tumour suppressor mutated in medulloblastoma, is central player Hh signalling, pathway crucial for development and deregulated cancer. Although the control Gli transcription factors by SuFu critical our understanding mechanism regulating this key event remains limited. Here, we show that Itch/β-arrestin2 complex binds induces its Lys63-linked polyubiquitylation without affecting stability. This process increases association with Gli3, promoting conversion Gli3...
Abstract The Hedgehog (Hh) pathway is essential for embryonic development and tissue homeostasis. Aberrant Hh signaling may occur in a wide range of human cancers, such as medulloblastoma, the most common brain malignancy childhood. Here, we identify endoplasmic reticulum aminopeptidase 1 (ERAP1), key regulator innate adaptive antitumor immune responses, previously unknown player pathway. We demonstrate that ERAP1 binds deubiquitylase enzyme USP47, displaces USP47-associated βTrCP,...
Article2 September 2019Open Access Source DataTransparent process Cyclin F-dependent degradation of E2F7 is critical for DNA repair and G2-phase progression Ruixue Yuan orcid.org/0000-0001-9813-6683 Department Pathobiology, Faculty Veterinary Medicine, Utrecht University, Utrecht, The Netherlands Search more papers by this author Qingwu Liu Hendrika A Segeren orcid.org/0000-0002-8115-6482 Laurensia Yuniati Hubrecht Institute-KNAW University Medical Center Daniele Guardavaccaro Biotechnology,...