A5057647262- Cancer-related Molecular Pathways
- Cancer Cells and Metastasis
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Hedgehog Signaling Pathway Studies
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Developmental Biology and Gene Regulation
- Cellular transport and secretion
- DNA and Nucleic Acid Chemistry
- Reproductive Biology and Fertility
- Tissue Engineering and Regenerative Medicine
- Signaling Pathways in Disease
- Pluripotent Stem Cells Research
- Bioinformatics and Genomic Networks
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Cancer, Stress, Anesthesia, and Immune Response
- Protein Kinase Regulation and GTPase Signaling
- Infectious Diseases and Mycology
- Immune cells in cancer
- Ubiquitin and proteasome pathways
European Institute of Oncology
2008-2022
Istituti di Ricovero e Cura a Carattere Scientifico
2019-2022
IFOM
2008-2018
Ripamonti
2008
Istituto di Genetica Molecolare
2004-2006
Notch signaling regulates cell specification and homeostasis of stem compartments, it is counteracted by the fate determinant Numb. Both Numb have been implicated in human tumors. Here, we show that altered approximately one third non–small-cell lung carcinomas (NSCLCs), which are leading cause cancer-related deaths: ≈30% NSCLCs, loss expression leads to increased activity, while a smaller fraction cases (around 10%), gain-of-function mutations NOTCH-1 gene present. Activation correlates...
The cell fate determinant Numb orchestrates tissue morphogenesis and patterning in developmental systems. In the human mammary gland, is a tumor suppressor regulates p53 levels. However, whether this function linked to its role determination remains unclear. Here, by exploiting an ex vivo system, we show that at mitosis of purified stem cells (SCs), ensures asymmetric outcome self-renewing divisions partitioning into progeny retains SC identity, where it sustains high activity. also controls...
The cis-acting elements necessary for the activity of DNA replication origins in metazoan cells are still poorly understood. Here we report a thorough characterization sequence requirements origin associated with human lamin B2 gene. A 1.2-kb segment, comprising start site and located within large protein-bound region, as well CpG island, displays when moved to different ectopic positions. Genomic footprinting analysis both endogenous indicates that protein complex is assembled cases around...
NUMB is a tumor suppressor gene that functions by inhibiting the action of NOTCH proto-oncogene and enhancing levels activity protein p53. In breast cancer (BC), loss-of-function (LOF), mediated various molecular mechanisms, frequent causal event. Herein, we establish loss protein, resulting from hyper-degradation, prevalent mechanism LOF in BC. Through RNAi-based screening, identified CRL7FBXW8 complex as E3 ligase responsible for hyper-degradation Genetic pharmacological inhibition rescued...
Numb functions as an oncosuppressor by inhibiting Notch signaling and stabilizing p53. This latter effect depends on the interaction of with Mdm2, E3 ligase that ubiquitinates p53 commits it to degradation. In breast cancer (BC), loss results in a reduction p53-mediated responses including sensitivity genotoxic drugs maintenance homeostasis stem cell compartment. this study, we show Numb-Mdm2 represents fuzzy complex mediated short sequence encompassing its alternatively spliced exon 3...
The endocytic protein NUMB has been implicated in the control of various polarized cellular processes, including acquisition mesenchymal migratory traits through molecular mechanisms that have only partially defined. Here, we report is a negative regulator specialized set understudied, apically restricted, actin-based protrusions, circular dorsal ruffles (CDRs), induced by either PDGF or HGF stimulation. Through its PTB domain, binds directly to an N-terminal NPLF motif ARF6 guanine...
Asymmetric cell division is a key tumor suppressor mechanism that prevents the uncontrolled expansion of stem (SC) compartment by generating daughter cells with alternative fates: one retains SC identity and enters quiescence other becomes rapidly proliferating differentiating progenitor. A critical player in this process Numb, which partitions asymmetrically at mitosis inflicts different proliferative differentiative fates two daughters. Here, we show asymmetric Numb partitioning per se...
Rac3, a neuronal GTP-binding protein of the Rho family, induces neuritogenesis in primary neurons. Using yeast two-hybrid analysis, we show that Neurabin I, F-actin binding protein, is direct Rac3-interacting molecule. Biochemical and light microscopy studies indicate I copartitions colocalizes with Rac3 at growth cones neurites, inducing association to cytoskeleton. Moreover, antisense oligonucleotides abolish Rac3-induced neuritogenesis, which turn rescued by exogenous but not mutant...
Abstract MDM2 regulates a variety of cellular processes through its dual protein:protein interaction and ubiquitin ligase activities. One major function is to bind ubiquitinate P53, thereby regulating proteasomal degradation. This in turn controlled by the cell fate determinant NUMB, which binds inhibits via short stretch 11 amino acids, contained phosphotyrosine-binding (PTB) domain, encoded exon 3 NUMB gene. The NUMB-MDM2-P53 circuitry relevant specification stem subversion has been shown...