4 research outputs found
Child maltreatment: medico-legal consultations at Spedali Civili Hospital of Brescia in 2011-2021 period
Integrating Rio1 activities discloses its nutrient-activated network in Saccharomyces cerevisiae
The Saccharomyces cerevisiae kinase/adenosine triphosphatase Rio1 regulates rDNA transcription and segregation, pre-rRNA processing and small ribosomal subunit maturation. Other roles are unknown. When overexpressed, human ortholog RIOK1 drives tumor growth and metastasis. Likewise, RIOK1 promotes 40S ribosomal subunit biogenesis and has not been characterized globally. We show that Rio1 manages directly and via a series of regulators, an essential signaling network at the protein, chromatin and RNA levels. Rio1 orchestrates growth and division depending on resource availability, in parallel to the nutrient-activated Tor1 kinase. To define the Rio1 network, we identified its physical interactors, profiled its target genes/transcripts, mapped its chromatin-binding sites and integrated our data with yeast's protein-protein and protein-DNA interaction catalogs using network computation. We experimentally confirmed network components and localized Rio1 also to mitochondria and vacuoles. Via its network, Rio1 commands protein synthesis (ribosomal gene expression, assembly and activity) and turnover (26S proteasome expression), and impinges on metabolic, energy-production and cell-cycle programs. We find that Rio1 activity is conserved to humans and propose that pathological RIOK1 may fuel promiscuous transcription, ribosome production, chromosomal instability, unrestrained metabolism and proliferation; established contributors to cancer. Our study will advance the understanding of numerous processes, here revealed to depend on Rio1 activity
Cnn1 inhibits the interactions between the KMN complexes of the yeast kinetochore
El pdf del artículo es la versión de autor.-- et al.Kinetochores attach the replicated chromosomes to the mitotic spindle and orchestrate their transmission to the daughter cells. Kinetochore-spindle binding and chromosome segregation are mediated by the multi-copy KNL1 Spc105, MIS12 Mtw1 and NDC80 Ndc80 complexes that form the so-called KMN network. KMN-spindle attachment is regulated by the AuroraB Ipl1 and MPS1 Mps1 kinases. It is unclear whether other mechanisms exist that support KMN activity during the cell cycle. Using budding yeast, we show that kinetochore protein Cnn1 localizes to the base of the Ndc80 complex and promotes a functionally competent configuration of the KMN network. Cnn1 regulates KMN activity in a spatiotemporal manner by inhibiting the interaction between its complexes. Cnn1 activity peaks in anaphase and is driven by the Cdc28, Mps1 and Ipl1 kinases. © 2012 Macmillan Publishers Limited. All rights reserved.P.D.W. acknowledges financial support from the Italian Association for Cancer Research (grant 8840). T.R.H. recognizes support from the N.I.H. (grant GM087461) and the American Cancer Society (grant IRG 58-006-50). T.U.T. acknowledges a Cancer Research U.K. senior fellowship and Wellcome Trust program grant. L.J.B. acknowledges a doctoral fellowship from the European School of Molecular Medicine.Peer Reviewe